The impact of age and obesity on outcomes among patients hospitalized with COVID-19 in Denmark: A nationwide cohort study

Purpose: Obesity may alter the severity of infection with Coronavirus disease 2019 (COVID-19). Age may impact the association between body weight and severity of COVID-19 in patients with obesity. The aim of the study was to examine the association between obesity and severity of infection in a Danish cohort hospitalized with COVID-19 in the initial wave of the pandemic. Patients and Methods: Based on data from the nationwide, clinical database: COVID-DK, risks of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and mortality were compared among patients with and without obesity. Interaction with age was examined and we used Inverse Probability of Treatment Weighting regression for confounder adjustment. Result(s): Among 524 patients, 142 (27%) were admitted to the ICU, 112 (21%) required IMV, and 109 (21%) died. Compared to COVID-19 patients without obesity, patients with obesity displayed a non-significant increased risk of ICU admission (Relative Risk [RR] 1.19, 95% Confidence Interval [CI] 0.88;1.60), IMV (RR 1.23, CI 0.86;1.75) and mortality (RR 1.21, CI 0.84;1.75). COVID-19 patients with obesity, <60 years had highly increased risk of ICU admission (RR 1.92, CI 1.14;3.24) and IMV (RR 1.95, CI 1.09;3.49). Conclusion(s): In hospitalized COVID-19 patients, obesity conferred an approximately 20% increased risk for ICU admission, IMV, and death, although these relationships did not reach statistical significance. COVID-19 patients with obesity and <60 years had an almost doubled risk of ICU admission and IMV. Copyright © 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.

ANTIBODY AND T-CELL RESPONSE SIX MONTHS AFTER INITIATION OF BNT162B2 VACCINATION IN PATIENTS WITH MULTIPLE MYELOMA OR CHRONIC LYMPHATIC B-CELL LEUKEMIA COMPARED TO HEALTHY CONTROLS

Background: The ongoing COVID-19 pandemic has resulted in more than 419 million cases and more than 5.9 million deaths. Preious studies hae indicated inferior responses to SARS-CoV-2 accination across different hematological diseases. Through this prospectie cohort study, we examined the deelopment and durability of anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients with either multiple myeloma (MM) or Chronic Lymphatic B-cell Leukemia (B-CLL) six months after accination and compared to immunocompetent controls. Aims: We aimed to inestigate the durability of immune responses to COVID-19 accination in patients with MM or B-CLL compared to healthy controls, and to identify risk factors for humoral non-response, including type of diagnosis. Methods: We measured anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients (MM: n=78, B-CLL: n=101) and 179 age and sex matched healthy controls up to six months after first accination. Anti- RBD IgG leels and neutralizing capacity of antibodies were measured at first and second dose of BNT162b2 and two and six months after first dose. Humoral response was defined as anti-RBD IgG > 225 AU/mL with a neutralizing index ≥ 25%. Humoral non-response was defined as the absence of a humoral response. T-cell responses were assessed six months after the first dose using an ELISA-based interferon-gamma release assay. A positie T-cell response was defined as IFN-γ release > 200 mIU/mL. Data on diagnoses were obtained through medical records, and data on accination status were obtained from the Danish Vaccination Register. Results: In patients with MM or B-CLL, the geometric mean concentration (GMC) of anti-RBD IgG increased from baseline 1.49 AU/mL (95% CI: 1.21-1.84) to three weeks after the first accine dose 15.10 AU/mL (95% CI: 9.39- 24.29) and after receiing the second dose 1179.60 AU/mL (95% CI: 727.78-1919.85). From two to six months after first accine there was a significant decline in the GMC of anti-RBD IgG to 252.75 AU/mL (95% CI: 159.17-403.43). The mean neutralizing capacity in patients with MM or B-CLL was lower than in controls at all time points after the first accine dose. Six months after first accine dose, 79 of 179 (44.1%) patients with MM or B-CLL had a positie humoral response, while this was the case for 170 of 179 controls (95.0%), p<0.001. Haing MM or B-CLL was significantly associated with risk of humoral non-response. This was most pronounced in B-CLL patients who had an age and sex adjusted risk ratio (RR) of 12.25 (95% CI: 6.42-23.38, p< 0.001) of humoral non-response compared to healthy controls. For MM patients the RR was 4.65 (95% CI: 2.21-9.80, p< 0.001). T-cell response was assessed in a subset of 48 patients with MM (n=28) or B-CLL (n=20) and 26 controls, six months after first accine dose. A total of 21 (43.8%) patients with MM (12/28) or B-CLL (9/20) and 14 (53.8%) controls had a positie T-cell response (p =0.56). Seen of 20 (35.0%) patients with MM or B-CLL who did not deelop a humoral response, deeloped a T-cell response (MM: 3/8, B-CLL: 4/12), while 14 of 28 (50.0%) patients with MM or B-CLL who deeloped a humoral response deeloped a T-cell response (p =0.46, MM: 9/11, B-CLL: 5/8). In healthy controls 14 of 25 (56.0%) people who deeloped a humoral response also deeloped a T-cell response. Summary/Conclusion: Humoral response to BNT162b2 was impaired in patients with MM or B-CLL compared to healthy controls. Both patients with MM and B-CLL were at higher risk of humoral non-response compared to healthy controls.

ANTIBODIES in SOLID ORGAN TRANSPLANT RECIPIENTS 6 MONTHS after BNT162b2 VACCINATION

Background: Previous studies have shown an inferior response to mRNA SARS-CoV-2 vaccination in solid organ transplant (SOT) recipients up to four months after vaccination. We examined the development in anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in SOT recipients six months after vaccination compared to immunocompetent controls. Methods: in 200 SOT recipients and 200 age-and sex-matched controls, we measured immunogenicity of two doses of BNT162b2 vaccine up to 6 months after vaccination. An in-house enzyme-linked immunosorbent assay (ELISA) based system was used to measure concentrations of anti-receptor binding domain (RBD) IgG. Neutralizing capacity of antibodies was estimated using an in-house ELISA based pseudo-neutralization assay. Presence of anti-SARS-CoV-2 nucleocapsid (N) antibodies was assessed using an electrochemiluminescence based kit from Roche diagnostics. Presence of N-antibodies was used as evidence of previous natural infection. In a subset of participants an interferon-gamma releasing assay was used to assess T-cell responses. Results: SOT recipients and controls demonstrated an increase in anti-RBD IgG after both first and second dose of BNT162b2. Six months after the first dose, GMC of anti-RBD IgG declined in both groups but remained higher in controls (55.85 AU/mL, 95% CI 36.95-83.33 vs. 1448.94 AU/mL, 95% CI 1139.43-1799.48). Furthermore, more controls had a cellular response six months after vaccination (13.1% of SOT recipients vs. 59.4% of controls, p<0.001). We found increasing age (RR 1.23 pr year, 95% CI 1.11-1.35, p<0.001), being within one year of transplantation (RR 1.55, 95% CI 1.30-1.85, p<0.001), use of mycophenolate (RR 1.53, 95% CI 1.18-1.99 p=0.001), kidney transplanation (RR 1.70, 95% CI 1.25-2.30, p=0.001), lung-transplantation (RR 1.63, 95% CI 1.16-2.29, p=0.005) and cancer comorbidity (RR 1.52, 95% CI 1.26-1.82, p <0.001) to be significantly associated with humoral non-response. Conclusion: Humoral and cellular responses to two doses of BNT162b2 are inferior in SOT recipients compared to controls. Furthermore, anti-RBD concentration decline 6 months after first vaccine dose. Further investigations of clinical significance of anti-RBD IgG concentration and vaccine non-response is warranted to optimize the timing and use of booster vaccines. Multiple risk factors for non-response were identified and may help identify SOT recipients at high risk of vaccine non-response.

[Cognitive late sequelae of COVID-19]

Cognitive sequelae of COVID-19 including memory and concentration difficulties have been observed in 40-65% of persons who have been hospitalised with COVID-19 and 27-50% of non-hospitalised individuals. The cognitive impairments are associated with reduced work function and quality of life. This review recommends systematic cognition screening at long-COVID clinics using brief and feasible objective cognitive screeners, such as the Screen for Cognitive Impairment in Psychiatry (SCIP) and Trail Making Test B or similar tests with sensitivity to cognitive impairment in young populations.

SARS-CoV-2 serosurvey among adults involved in healthcare and health research in Guinea-Bissau, West Africa.

OBJECTIVES: Many African countries have reported fewer COVID-19 cases than countries elsewhere. By the end of 2020, Guinea-Bissau, West Africa, had <2500 PCR-confirmed cases corresponding to 0.1% of the ∼1.8 million national population. We assessed the prevalence of SARS-CoV-2 antibodies in urban Guinea-Bissau to help guide the pandemic response in Guinea-Bissau. STUDY DESIGN: Cross-sectional assessment of SARS-CoV-2 antibody in a cohort of staff at the Bandim Health Project. METHODS: We measured IgG antibodies using point-of-care rapid tests among 140 staff and associates at a biometric research field station in Bissau, the capital of Guinea-Bissau, during November 2020. RESULTS: Of 140 participants, 25 (18%) were IgG-positive. Among IgG-positives, 12 (48%) reported an episode of illness since the onset of the pandemic. Twenty-five (18%) participants had been PCR-tested between May and September; 7 (28%) had been PCR-positive. Four of these seven tested IgG-negative in the present study. Five participants reported that somebody had died in their house, corresponding crudely to an annual death rate of 4.5/1000 people; no death was attributed to COVID-19. Outdoor workers had a lower prevalence of IgG-positivity. CONCLUSIONS: In spite of the low official number of COVID-19 cases, our serosurvey found a high prevalence of IgG-positivity. Most IgG-positives had not been ill. The official number of PCR-confirmed COVID-19 cases has thus grossly underestimated the prevalence of COVID-19 during the pandemic. The observed overall mortality rate in households of Bandim Health Project employees was not higher than the official Guinean mortality rate of 9.6/1000 people.

Retrospective epidemiological analysis of SARS-CoV-2 wastewater surveillance and case notifications data - New South Wales, Australia, 2020.

This epidemiological study analysed SARS-CoV-2 wastewater surveillance and case notifications data to inform evidence-based public health action in NSW. We investigated measures of association between SARS-CoV-2 RNA fragments detected in wastewater samples (n = 100) and case notifications (n = 1,367, as rates per 100,000 population) within wastewater catchment areas (n = 6); and evaluated the performance of wastewater testing as a population-level diagnostic tool. Furthermore, we modelled SARS-CoV-2 RNA fragment detection in wastewater given the case notification rate using logistic regression. The odds of a viral detection in wastewater samples increased by a factor of 5.68 (95% CI: 1.51-32.1, P = 0.004) with rates of one or more notified cases within a catchment. The diagnostic specificity of wastewater viral detection results was 0.88 (95% CI: 0.69-0.97); the overall diagnostic sensitivity was 0.44 (95% CI: 0.33-0.56). The probability of a viral detection result in wastewater exceeded 50% (95% CI: 36-64%) once the case rate within a catchment exceeded 10.5. Observed results suggest that in a low prevalence setting, wastewater viral detections are a more reliable indicator of the presence of recent virus shedding cases in a catchment, than non-detect results are of the absence of cases in a catchment.

Cognitive impairments four months after COVID-19 hospital discharge: Pattern, severity and association with illness variables.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has affected more than 100 million people and clinics are being established for diagnosing and treating lingering symptoms, so called long-COVID. A key concern are neurological and long-term cognitive complications. At the same time, the prevalence and nature of the cognitive sequalae of COVID-19 are unclear. The present study aimed to investigate the frequency, pattern and severity of cognitive impairments 3-4 months after COVID-19 hospital discharge, their relation to subjective cognitive complaints, quality of life and illness variables. We recruited patients at their follow-up visit at the respiratory outpatient clinic, Copenhagen University Hospital, Bispebjerg, approximately four months after hospitalisation with COVID-19. Patients underwent pulmonary, functional and cognitive assessments. Twenty-nine patients were included. The percentage of patients with clinically significant cognitive impairment ranged from 59% to 65% depending on the applied cut-off for clinical relevance of cognitive impairment, with verbal learning and executive functions being most affected. Objective cognitive impairment scaled with subjective cognitive complaints, lower work function and poorer quality of life. Cognitive impairments were associated with d-dimer levels during acute illness and residual pulmonary dysfunction. In conclusion, these findings provide new evidence for frequent cognitive sequelae of COVID-19 and indicate an association with the severity of the lung affection and potentially restricted cerebral oxygen delivery. Further, the associations with quality of life and functioning call for systematic cognitive screening of patients after recovery from severe COVID-19 illness and implementation of targeted treatments for patients with persistent cognitive impairments.