In an add-on study of the WHO Solidarity trial, Norwegian investigators examined the effect of remdesivir and hydroxychloroquine on the degree of clinical respiratory failure, on SARS-CoV-2 viral load in the oropharynx, and on levels of inflammatory variables in plasma or serum.

Background The understanding of coronavirus disease 2019 (COVID-19) is rapidly evolving. Although it is primarily a respiratory illness, other manifestations, such as Guillain-Barré syndrome, immune thrombocytopenia, and immune-mediated thrombotic thrombocytopenic purpura, have been described. We present a case of a patient with hemophagocytic lymphohistiocytosis secondary to COVID-19 treated with tocilizumab with a marked biochemical improvement. Case presentation In this case report we present a Caucasian patient with COVID-19 who developed a marked elevation of inflammatory parameters with ferritin 36,023 μg/L, but also elevated C-reactive protein 334 mg/L and lactate dehydrogenase 1074 U/L, 1 week after admission to the intensive care unit. He met five of eight criteria for hemophagocytic lymphohistiocytosis, but he lacked the high fever and cytopenia seen in the majority of cases. He was treated with tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, and over the next days, a rapid decrease in ferritin and C-reactive protein levels was observed. However, his respiratory failure only improved gradually, and he was weaned off the respirator 11 days later. Conclusion COVID-19 may induce a hyperinflammatory clinical picture and in some cases develop into hemophagocytic lymphohistiocytosis. In our patient’s case, therapeutic interleukin-6 blockade abrogated signs of hyperinflammation but did not seem to improve pulmonary function. Measurement of ferritin and C-reactive protein, as well as quantification of interleukin-6 on indication, should be performed in patients with severe COVID-19. Specific treatment in such patients must also be contemplated, preferably in randomized controlled trials.

Summary Infection with coronavirus disease‐2019 (COVID‐19) may predispose for venous thromboembolism (VTE). There is wide variation in reported incidence rates of VTE in COVID‐19, ranging from 3% to 85%. Therefore, the true incidence of thrombotic complications in COVID‐19 is uncertain. Here we present data on the incidence of VTE in both hospitalised and non‐hospitalised patients from two ongoing prospective cohort studies. The incidence of VTE after diagnosis of COVID‐19 was 3·9% [95% confidence interval (CI): 2·1–7·2] during hospitalisation, 0·9% (95% CI: 0·2–3·1) in the three months after discharge and 0·2% (95% CI: 0·00–1·25) in non‐hospitalised patients, suggesting an incidence rate at the lower end of that in previous reports.

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Despite numerous studies on SARS-CoV-2induced inflammation, we still lack markers for rapid disease progression with admission to intensive care unit (ICU) or respiratory failure (RF). Few studies have evaluated the prognostic value of routine diagnostic repertoire available at most hospitals. The NOR-Solidarity trial is an independent add-on study to the WHO Solidarity trial, evaluating hydroxychloroquine (HCQ) and remdesivir compared to standard of care in hospitalized COVID-19 patients [1]. We explored whether standard biomarkers in peripheral blood could give information on ICU admission and RF in hospitalized COVID-19 patients.Adult patients admitted to 23 Norwegian hospitals with PCR-confirmed SARS-2-CoV-2 infection were eligible for participation. In this substudy, the routine biochemistry was related to (i) the need for ICU admission or (ii) RF defined as pO 2 /FiO 2 (P/F ratio) < 26.6 kPa during the first 10 days of hospitalization. Routine peripheral blood samples were collected at inclusion and daily until discharge from the hospital, and outpatients were followed up 3 months after discharge. Markers included were C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), haemoglobin, fibrinogen, procalcitonin (PCT), D-dimer, platelet count, total white blood cell count, monocyte, neutrophil and lymphocyte count. Exclusion criteria, intervention, ethical statement, details on viral load and SARS-CoV-2 antibodies and statistical analysis are given in the Supporting Information file.

Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score <-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8–13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4–14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6–9 symptoms vs. 0–5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

IntroductionCOVID‐19 is associated with an increased risk of venous thromboembolism (VTE), but there is great variation among reported incidence rates. Most previous studies have focused on hospitalized patients with COVID‐19, and only a few reports are from population‐based registries.MethodsWe studied the 90‐day incidence of VTE, associated risk factors and all‐cause mortality in hospitalized and nonhospitalized patients with COVID‐19 in a nationwide cohort. Data on hospitalizations and outpatient visits were extracted from two national registries with mandatory reporting linked by a unique national identification number carried by all Norwegian residents. We performed Cox proportional hazards regression to determine risk factors for VTE after infection with SARS‐CoV‐2.ResultsOur study included 30,495 patients with positive SARS‐CoV‐2 polymerase chain reaction with a mean (SD) age of 41.9 (17.3) years, and 53% were males. Only 2081 (6.8%) were hospitalized. The 90‐day incidence of VTE was 0.3% (95% CI: 0.21–0.33) overall and 2.9% (95% CI: 2.3–3.7) in hospitalized patients. Age (hazard ratio [HR] 1.28 per decade, 95% CI: 1.11–1.48, p < 0.05), history of previous VTE (HR 4.69, 95% CI: 2.34–9.40, p < 0.05), and hospitalization for COVID‐19 (HR 23.83, 95% CI: 13.48–42.13, p < 0.05) were associated with risk of VTE.ConclusionsThe 90‐day incidence of VTE in hospitalized and nonhospitalized patients with COVID‐19 was in the lower end compared with previous reports, with considerably higher rates in hospitalized than nonhospitalized patients. Risk factors for VTE were consistent with previously reported studies.

Introduction The incidence of thromboembolism during COVID-19 and the use of thromboprophylaxis vary greatly between studies. Only a few studies have investigated the rate of thromboembolism post-discharge. This study determined the 90-day incidence of venous and arterial thromboembolic complications, risk factors for venous thromboembolic events and characterized the use of thromboprophylaxis during and after hospitalization. Materials and methods We retrospectively reviewed medical records for adult patients hospitalized for >24 hours for COVID-19 before May 15, 2020, in ten Norwegian hospitals. We extracted data on demographics, thromboembolic complications, thromboembolic risk factors, and the use of thromboprophylaxis. Cox proportional hazards regression was used to determine risk factors for VTE. Results 550 patients were included. The 90-day incidence of arterial and venous thromboembolism in hospitalized patients was 6.9% (95% CI: 5.1–9.3) overall and 13.8% in the ICU. Male sex (hazard ratio (HR) 7.44, 95% CI 1.73–32.02, p = 0.007) and previous VTE (HR 6.11, 95% CI: 1.74–21.39, p = 0.005) were associated with risk of VTE in multivariable analysis. Thromboprophylaxis was started in 334 patients (61%) with a median duration of 7 days (25th–75th percentile 3–13); in the VTE population 10/23 (43%) started thromboprophylaxis prior to diagnosis. After discharge 20/223 patients received extended thromboprophylaxis and 2/223 (0.7%, 95% CI: 0.3–1.9) had a thromboembolism. Conclusions The 90-day incidence of thromboembolism in COVID-19 patients was 7%, but <1% after discharge. Risk factors were male sex and previous VTE. Most patients received thromboprophylaxis during hospitalization, but only <10% after discharge.