SARS CoV-2 Infection among Health Care Workers from Different Health Care Facilities in Western Norway: A Prospective, Cross-Sectional Study.

Background: Comparative data on COVID-19 among health care workers (HCWs) in different health care settings are scarce. This study investigated the rates of previous COVID-19 among HCWs in nursing homes, hospitals and a municipal emergency room (ER). Methods: We prospectively included 747 HCWs: 313 from nursing homes, 394 from hospitals and 40 from the ER. The diagnosis of COVID-19 was based on serological evidence of SARS-CoV-2 antibody positivity and self-reported RT-PCR positivity prior to inclusion. Information regarding age, sex and exposure to SARS-CoV-2 infection was collected. Results: A total of 4% (11/313) of nursing home HCWs and 6% (28/434) of HCWs in hospitals/the ER tested positive by serology and/or RT-PCR (p = 0.095). Fewer HCWs in nursing homes had occupational exposure to SARS-CoV-2 compared to those in hospitals/the ER (16% vs. 48%, p < 0, 001), but nursing homes had a higher proportion of HCWs with occupational exposure using partial/no PPE (56% vs. 19%, p < 0.001). Nevertheless, no significant differences in the risk for COVID-19 were found in relation to the rate of occupational exposure (p = 0.755) or use of inadequate PPE (p = 0.631). Conclusions: Despite a small sample size, the risk for COVID-19 among HCWs did not appear to be related to the type of health care facility, rates of occupational exposure or use of PPE.

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.

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.

Lower antibiotic prescription rates in hospitalized COVID-19 patients than influenza patients, a prospective study.

BACKGROUND: COVID-19 patients are extensively treated with antibiotics despite few bacterial complications. We aimed to study antibiotic use in hospitalized COVID-19 patients compared to influenza patients in two consecutive years. Furthermore, we investigated changes in antibiotic use from the first to second pandemic wave. METHODS: This prospective study included both patients from two referral hospitals in Bergen, Norway, admitted with influenza (n = 215) during the 2018/2019 epidemic and with COVID-19 (n = 82) during spring/summer 2020, and national data on registered Norwegian COVID-19 hospital admissions from March 2020 to January 2021 (n = 2300). Patient characteristics were compared, and logistic regression analysis was used to identify risk factors for antibiotic use. RESULTS: National and local COVID-19 patients received significantly less antibiotics (53% and 49%) than influenza patients (69%, p < .001). Early antibiotics contributed to >90% of antibiotic prescriptions in the two local hospitals, and >70% of prescriptions nationally. When adjusted for age, comorbidities, symptom duration, chest X-ray infiltrates and oxygen treatment, local COVID-19 patients still had significantly lower odds of antibiotic prescription than influenza patients (aOR 0.21, 95%CI 0.09-0.50). At the national level, we observed a significant reduction in antibiotic prescription rates in the second pandemic wave compared to the first (aOR 0.35, 95% CI 0.29-0.43). CONCLUSION: Fewer COVID-19 patients received antibiotics compared to influenza patients admitted to the two local hospitals one year earlier. The antibiotic prescription rate was lower during the second pandemic wave, possibly due to increased clinical experience and published evidence refuting the efficacy of antibiotics in treating COVID-19 pneumonia.

Long COVID in a prospective cohort of home-isolated patients.

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients-247 home-isolated and 65 hospitalized-comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

Nursing home deaths after COVID-19 vaccination. / Dødsfall i sykehjem etter covid-19-vaksine.

BACKGROUND: In the period 27 December 2020 to 15 February 2021, about 29 400 of Norway's roughly 35 000 nursing home patients were vaccinated with the mRNA vaccine BNT162b2. During the same period, the Norwegian Medicines Agency received 100 reports of suspected fatal adverse reactions to the vaccine. An expert group has examined the reports and assessed the extent of a causal link between vaccination and death. MATERIAL AND METHOD: The expert group worked in two pairs, each of which examined 50 anonymised reports. Each member first examined the reports alone and classified the causality as unlikely, possible, probable, certain or unclassifiable. Each pair then discussed their results until they reached a consensus. All four experts assessed a random sample of 20 reports. The degree of agreement was assessed using weighted kappa and McNemar's test of symmetry. RESULTS: The mean age of the patients was 87.7 years (range 61-103 years). Among 100 reported deaths, a causal link to the vaccine was considered probable in 10 cases, possible in 26 and unlikely in 59. Five were unclassifiable. Weighted kappa was 0.40 and 0.38 in the two expert pairs, respectively. INTERPRETATION: Most nursing home patients have a short remaining life expectancy, but vaccination may, in a few cases, have accelerated a process of dying that had already begun. Nursing home patients should still be given priority for vaccination, but the benefits versus risk must be carefully weighed up for the frailest patients.

Should all nursing home residents be vaccinated? / Bør alle sykehjemsbeboere vaksineres?

Some frail nursing home residents in Norway have died after being vaccinated against COVID-19. Vaccination is an important measure for preventing outbreaks and deaths in nursing homes, but some of the frailest residents with serious health problems should not be vaccinated.

Outbreak of COVID-19 at three nursing homes in Bergen. / Utbrudd av covid-19 ved tre sykehjem i Bergen.

BACKGROUND: Nursing home residents are generally old and frail, and at high risk that COVID-19 will take a serious course. Outbreaks of COVID-19 have not previously been described in Norway, and it is important to identify mechanisms for spread of the infection and course of disease for nursing home residents with this pandemic disease. MATERIAL AND METHOD: We included residents from three nursing homes with outbreaks of COVID-19 in a retrospective observational study, and we retrieved information on the number of staff for whom SARS-CoV-2 was confirmed or who were placed in quarantine. We present resident characteristics, course of disease and mortality associated with COVID-19 in the nursing homes, as well as providing a brief description of the outbreaks. RESULTS: Forty residents were included, 26 of whom were women. The average age was 86.2 years. Thirty-seven of the residents had atypical symptoms, nine of them were asymptomatic at the time of diagnosis, and 21 died during the coronavirus infection. Contact tracing indicated that the outbreaks may have originated from staff in the pre-symptomatic or early and mild phase of the disease. SARS-CoV-2 was detected in forty-two staff members, and a further 115 were placed in quarantine. INTERPRETATION: Many residents had atypical disease presentation, and the mortality from COVID-19 was high. Spread of infection may have originated from staff, also before they displayed obvious symptoms, and contributed to extensive spread of SARS-CoV-2 in the three nursing homes.