Symptom Burden and Immune Dynamics 6 to 18 Months Following Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2): A Case-control Study.

BACKGROUND: The burden and duration of persistent symptoms after nonsevere coronavirus disease 2019 (COVID-19) remains uncertain. This study aimed to assess postinfection symptom trajectories in home-isolated COVID-19 cases compared with age- and time- matched seronegative controls, and investigate immunological correlates of long COVID. METHODS: A prospective case-control study included home-isolated COVID-19 cases between February 28 and April 4, 2020, and followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive controls. We collected clinical data at baseline, 6, 12, and 18 months postinfection, and blood samples at 2, 4, 6, and 12 months for analysis of SARS-CoV-2-specific humoral and cellular responses. RESULTS: Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared with controls, adult cases had a high risk of fatigue (27% excess risk, sex, and comorbidity adjusted odds ratio [aOR] 5.86; 95% confidence interval [CI], 3.27-10.5), memory problems (21% excess risk; aOR 7.42; CI, 3.51-15.67), concentration problems (20% excess risk; aOR 8.88; 95% CI, 3.88-20.35), and dyspnea (10% excess risk; aOR 2.66; 95% CI, 1.22-5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%; 95% CI, 1.5-21.5; P = .024) and among women (excess risk 18.7%; 95% CI, 4.4-32.9; P = .010). Longitudinal spike immunoglobulin G was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4+ T-cell receptor ß depth was significantly associated with both dyspnea and number of symptoms at 12 months. CONCLUSIONS: This study documents a high burden of persisting symptoms after mild COVID-19 and suggests that infection induced SARS-CoV-2-specific immune responses may influence long-term symptoms.

Durable T-cellular and humoral responses in SARS-CoV-2 hospitalized and community patients.

BACKGROUND: Neutralizing antibodies are important for protection against the pandemic SARS-CoV-2 virus, and long-term memory responses determine the risk of re-infection or boosting after vaccination. T-cellular responses are considered important for partial protection against novel variants of concern. METHODS: A prospective cohort of hospitalized (n = 14) and community (n = 38) patients with rt-PCR confirmed SARS-CoV-2 infection were recruited. Blood samples and clinical data were collected when diagnosed and at 6 months. Serum samples were analyzed for SARS-CoV-2-spike specific antibodies using ELISA (IgG, IgA, IgM), pseudotype neutralization and microneutralization assays. Peripheral blood mononuclear cells were investigated for virus-specific T-cell responses in the interferon-γ and interleukin-2 fluorescent-linked immunosorbent spot (FluroSpot) assay. RESULTS: We found durable SARS-CoV-2 spike- and internal protein specific T-cellular responses in patients with persistent antibodies at 6 months. Significantly higher IL-2 and IFN-γ secreting T-cell responses as well as SARS-CoV-2 specific IgG and neutralizing antibodies were detected in hospitalized compared to community patients. The immune response was impacted by age, gender, comorbidity and severity of illness, reflecting clinical observations. CONCLUSIONS: SARS-CoV-2 specific T-cellular and antibody responses persisted for 6 months post confirmed infection. In previously infected patients, re-exposure or vaccination will boost long-term immunity, possibly providing protection against re-infection with variant viruses.

Point-of-Care Influenza Testing Impacts Clinical Decision, Patient Flow, and Length of Stay in Hospitalized Adults.

BACKGROUND: Influenza is difficult to distinguish clinically from other acute respiratory infections. Rapid laboratory diagnosis can help initiate early effective antiviral treatment and isolation. Implementing a novel point-of-care test (POCT) for influenza in the emergency department (ED) could improve treatment and isolation strategies and reduce the length of stay (LOS). METHODS: In a prospective, controlled observational cohort study, we enrolled patients admitted due to acute respiratory illness to 2 public hospitals in Bergen, Norway, one using a rapid POCT for influenza (n = 400), the other (n = 167) using conventional rapid laboratory-based assay. RESULTS: Prevalence of influenza was similar in the 2 hospitals (154/400, 38% vs 38%, 63/167; P = .863). Most patients in both hospitals received antiviral (83% vs 81%; P = .703) and antibiotic treatment (72% vs 62%; P = .149). Isolation was more often initiated in ED in the hospital using POCT (91% vs 80%; P = .025). Diagnosis by POCT was associated with shorter hospital stay; old age, diabetes, cancer, and use of antibiotics, particularly broad-spectrum antibiotics, were associated with prolonged stay. CONCLUSIONS: POCT implementation in ED resulted in improved targeted isolation and shorter LOS. Regardless of POCT use, most influenza patients received antivirals (>80%) and antibiotics (>69%).

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.