Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. METHODS: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene. RESULTS: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months. CONCLUSION: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.

Subacute thyroiditis after COVID-19. / Subakutt tyreoiditt etter covid-19.

BACKGROUND: Since the beginning of the pandemic we have learned much about acute organ complications due to COVID-19, but we are still only beginning to understand the post-infection complications. CASE PRESENTATION: A man in his forties was diagnosed with subacute thyroiditis after a mild COVID-19 infection. This is an important differential diagnosis to consider if after a period of improvement, an infected patient develops fever, pain around the region of the thyroid (throat/neck) and/or symptoms of hyperthyroidism. INTERPRETATION: Subacute thyroiditis is thought to be initiated by a viral infection or postviral inflammatory process, often in patients with a history of an upper respiratory infection typically two to eight weeks prior to the onset of thyroiditis. The condition is believed to be triggered by an antigen created by the virus. Subacute thyroiditis must be on the list of possible differential diagnoses in patients with COVID-19 whose condition deteriorates after a period of improvement.

Seventy patients treated for COVID-19 by Østfold Hospital Trust. / 70 pasienter med covid-19 innlagt ved Sykehuset Østfold.

BACKGROUND: There is a need for further data on the COVID-19 situation in Norway. Our aim was to describe the patients admitted to our local hospital with COVID-19 in the spring of 2020. MATERIAL AND METHOD: Data were retrieved retrospectively from our local quality register for COVID-19 and include all patients admitted to Østfold Hospital in the period 10 March 2020-31 May 2020. RESULTS: A total of 70 patients were admitted, of whom 47 (67 %) were men. The mean age was 59 years (range 18-95). The most common comorbid conditions were obesity (n = 22, 31 %), chronic coronary artery disease (n = 21, 30 %) and diabetes (n = 17, 24 %). Thirteen patients (19 %) had no comorbidities. The most common symptoms were cough (n = 56, 80 %), dyspnoea (n = 51, 73 %) and fever (n = 48, 69 %). The most frequent complications were cardiac manifestations (n = 18, 26 %), acute respiratory distress syndrome (n = 14, 20 %) and acute kidney injury (n = 9, 13 %). Four (6 %) patients developed venous thromboembolism. Twenty patients (29 %) became critically ill. Thirteen (19 %) received treatment in the intensive care unit, and seven (10 %) died while in hospital. INTERPRETATION: Most of those admitted were middle-aged men. Many had no comorbidities. The most frequent non-respiratory complications were cardiac manifestations and kidney injury. A large proportion of patients became critically ill secondary to acute respiratory distress syndrome.

Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9.

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.