A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

SARS-CoV-2 vaccines are not associated with hypercoagulability in apparently healthy people.

Background: SARS-CoV-2 adenoviral-vector-DNA vaccines have been linked to the rare but serious thrombotic post-vaccine complication vaccine-induced immune thrombotic thrombocytopenia (VITT). This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. Objectives: To investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. Methods: This observational study included 567 healthcare personnel, 521 were recruited post-vaccination after a first dose of adenoviral vector ChAdOx1-S (Vaxzevria®, AstraZeneca) vaccine, and 46 prospectively before vaccination with an mRNA vaccine, either Spikevax® (Moderna, n=38) or Comirnaty® (Pfizer-BioNTech, n=8). In the mRNA group, samples were acquired before and 1-2 weeks after vaccination. In addition to pre-vaccination samples, 56 unvaccinated blood donors were recruited as controls (total n=102). Thrombin generation, D-dimer and free tissue factor pathway inhibitor (TFPI) were analyzed. Results: No participant experienced thrombosis, VITT or thrombocytopenia (platelet count <100·109/L) one week to one month post-vaccination. There was no increase in thrombin generation, D-dimer or TFPI in the ChAdOx1-S vaccine group compared with controls, or after the mRNA vaccines compared with baseline values. Eleven of 513 vaccinated with ChAdOx1-S (2.1%) had anti-PF4/polyanion antibodies without concomitant increase in thrombin generation. Conclusion: In this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer or TFPI levels compared with baseline or unvaccinated controls. These findings argue against subclinical activation of coagulation post-COVID-19 vaccination.

Cognitive function in non-hospitalized patients 8-13 months after acute COVID-19 infection: A cohort study in Norway.

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.

Thromboembolic complications during and after hospitalization for COVID-19: Incidence, risk factors and thromboprophylaxis

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.

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.

Incidence of thrombotic complications in hospitalised and non-hospitalised patients after COVID-19 diagnosis.

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.

An observational study to identify the prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in Norwegian health care workers after COVID-19 vaccination.

BACKGROUND: The COVID-19 vaccine from AstraZeneca (AZD1222) is one of several vaccines introduced to provide immunity against SARS-CoV-2. Recently, more than 50 cases have been reported presenting a combination of thrombosis, thrombocytopenia, and remarkably high levels of anti-platelet factor 4 (PF4)/polyanion antibodies post-AZD1222 vaccination. Now linked to the vaccine, the condition is referred to as vaccine-induced immune thrombotic thrombocytopenia. The European Medicines Agency still recommends vaccination with AZD1222, but several European countries have temporally paused and/or restricted its use because of the perceived risk of this severe side effect. Because there is no description of PF4/polyanion antibody testing in the clinical trials, knowledge about the prevalence of such antibodies in a vaccinated cohort is needed. OBJECTIVES: To investigate prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in a population recently vaccinated with AZD1222. PATIENTS/METHODS: Four hundred and ninety-two health care workers recently vaccinated with the first dose of AZD1222 were recruited from two hospitals in Norway. Study individuals were screened for thrombocytopenia and the presence of anti-PF4/polyanion antibodies with a PF4/PVS immunoassay. Side effects after vaccination were registered. RESULTS: The majority of study participants had normal platelet counts and negative immunoassay. Anti-PF4/polyanion antibodies without platelet activating properties were only detected in six individuals (optical density ≥0.4, range 0.58-1.16), all with normal platelet counts. No subjects had severe thrombocytopenia. CONCLUSIONS: We found low prevalence of both thrombocytopenia and antibodies to PF4/polyanion-complexes among Norwegian health care workers after vaccination with AZD1222.

Prevalence and Determinants of Fatigue after COVID-19 in Non-Hospitalized Subjects: A Population-Based Study.

This study assessed the prevalence and determinants of fatigue in a population-based cohort of non-hospitalized subjects 1.5-6 months after COVID-19. It was a mixed postal/web survey of all non-hospitalized patients ≥18 years with a positive PCR for SARS-CoV-2 until 1 June 2020 in a geographically defined area. In total, 938 subjects received a questionnaire including the Chalder fatigue scale (CFQ-11) and the energy/fatigue scale of the RAND-36 questionnaire. We estimated z scores for comparison with general population norms. Determinants were analyzed using multivariable logistic and linear regression analysis. In total, 458 subjects (49%) responded to the survey at median 117.5 days after COVID-19 onset, and 46% reported fatigue. The mean z scores of the CFQ-11 total was 0.70 (95% CI 0.58 to 0.82), CFQ-11 physical 0.66 (0.55 to 0.78), CFQ-11 mental 0.47 (0.35 to 0.59) and RAND-36 energy/fatigue -0.20 (-0.31 to -0.1); all CFQ-11 scores differed from those of the norm population (p < 0.001). Female sex, single/divorced/widowed, short time since symptom debut, high symptom load, and confusion during acute COVID-19 were associated with higher multivariable odds of fatigue. In conclusion, the burden of post-viral fatigue following COVID-19 was high, and higher than in a general norm population. Symptoms of fatigue were most prevalent among women, those having a high symptom load, or confusion during the acute phase.

Prevalence and Risk Factors for Post-Traumatic Stress in Hospitalized and Non-Hospitalized COVID-19 Patients.

This population-based study assessed the prevalence and determinants of symptom-defined post-traumatic stress disorder (PTSD) in a cohort of hospitalized and non-hospitalized patients about 1.5-6 months after their COVID-19 onset. The data were acquired from two mixed postal/web surveys in June-September 2020 from patients all aged ≥18 years with a positive polymerase chain reaction for severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) until 1 June 2020, comprising both hospitalized and non-hospitalized subjects. The catchment areas of the two included hospitals covers about 17% of the population of Norway. In total, 211 hospitalized and 938 non-hospitalized subjects received invitation. The prevalence of symptom-defined PTSD was assessed using the PTSD checklist for DSM-5 (PCL-5). Determinants of symptom-defined PTSD and PTSD symptoms were analyzed using multivariable logistic and linear regression analysis. In total, 583 (51%) subjects responded at median 116 (range 41-200) days after COVID-19 onset. The prevalence of symptom-defined PTSD was 9.5% in hospitalized and 7.0% in non-hospitalized subjects (p = 0.80). Female sex, born outside of Norway, and dyspnea during COVID-19 were risk factors for persistent PTSD symptoms. In non-hospitalized subjects, previous depression and COVID-19 symptom load were also associated with persistent PTSD symptoms. In conclusion, COVID-19 symptom load, but not hospitalization, was associated with symptom-defined PTSD and PTSD symptom severity.

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 symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study.

This study assessed symptoms and their determinants 1.5-6 months after symptom onset in non-hospitalised subjects with confirmed COVID-19 until 1 June 2020, in a geographically defined area. We invited 938 subjects; 451 (48%) responded. They reported less symptoms after 1.5-6 months than during COVID-19; median (IQR) 0 (0-2) versus 8 (6-11), respectively (p<0.001); 53% of women and 67% of men were symptom free, while 16% reported dyspnoea, 12% loss/disturbance of smell, and 10% loss/disturbance of taste. In multivariable analysis, having persistent symptoms was associated with the number of comorbidities and number of symptoms during the acute COVID-19 phase.