Surfactant protein D (SP-D) as a biomarker of SARS-CoV-2 infection.

BACKGROUND: Surfactant protein-D (SP-D) is a lung-resident protein that has emerged as a potential biomarker for COVID-19. Previous investigations on acute respiratory distress syndrome patients demonstrated a significant increment of SP-D serum levels in pathological conditions. Since SP-D is not physiologically permeable to alveoli-capillary membrane and poorly expressed by other tissues, this enhancement is likely due to an impairment of the pulmonary barrier caused by prolonged inflammation. METHODS: A retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio was conducted to assess differences of the hematic SP-D concentrations among COVID-19 patients and healthy donors and if SP-D levels resulted a risk factor for disease severity and mortality. RESULTS: The first analysis, using an ANOVA-model, showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors. Significant variations were also found between dead vs survived patients. Results confirm that SP-D concentrations were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. Further analysis conducted with Logistic Mixed models, highlighted that higher SP-D levels at admission and increasing differences among follow-up and admission values resulted the strongest significant risk factors of mortality (model predictive accuracy, AUC = 0.844). CONCLUSIONS: The results indicate that SP-D can be a predictive marker of COVID-19 disease and its outcome. Considering its prognostic value in terms of mortality, the early detection of SP-D levels and its follow-up in hospitalized patients should be considered to direct the therapeutic intervention.

Persisting Symptoms After COVID-19.

BACKGROUND: After recovering from coronavirus disease 2019 (COVID-19), a considerable number of patients report long-term sequelae. The epidemiologic data vary widely in the studies published to date, depending on the study design and the patient cohorts analyzed. Using a population-based approach, we report symptoms and clinical characteristics following COVID-19 (long COVID), focusing on symptoms ≥ 12 weeks (post-COVID-19). METHODS: In three German administrative districts, all adult patients with a diagnosis of COVID-19 confirmed by polymerase chain reaction (PCR) between March and September 2020 (n = 4632) were invited to complete a questionnaire. Predictors for post-COVID-19 were identified by multiple ordinal regression analysis. Study registration: DRKS00023069. RESULTS: A total of 1459 patients were included in the study, 175 (12%) of whom had been hospitalized for treatment of the acute phase of COVID-19. The prevalence of post-COVID-19 was 72.6% (n = 127) and 46.2% (n = 588) for hospitalized and non-hospitalized patients, respectively. The most frequently occurring long-term symptoms were fatigue (41.5% of all symptoms ≥ 12 weeks, n = 297), physical exhaustion (40.8%, n = 292), difficulty in concentrating (30.6%, n = 219), and loss of the senses of taste (25.9%, n = 185) and smell (25.5%, n = 182). Quality of life was significantly impaired in patients with post-COVID-19. The strongest risk factors for post-COVID-19 were female sex, overall severity of comorbidities, and severity of acute COVID-19. CONCLUSION: Patients who are not hospitalized also frequently experience continued symptoms following COVID-19. The heterogeneity of symptoms calls for a multi - disciplinary stepped-care approach, for which identification of patients at risk is crucial. A limitation of the study is the lack of a control group.

Full-Length Recombinant hSP-D Binds and Inhibits SARS-CoV-2.

SARS-CoV-2 infection of host cells is driven by binding of the SARS-CoV-2 spike-(S)-protein to lung type II pneumocytes, followed by virus replication. Surfactant protein SP-D, member of the front-line immune defense of the lungs, binds glycosylated structures on invading pathogens such as viruses to induce their clearance from the lungs. The objective of this study is to measure the pulmonary SP-D levels in COVID-19 patients and demonstrate the activity of SP-D against SARS-CoV-2, opening the possibility of using SP-D as potential therapy for COVID-19 patients. Pulmonary SP-D concentrations were measured in bronchoalveolar lavage samples from patients with corona virus disease 2019 (COVID-19) by anti-SP-D ELISA. Binding assays were performed by ELISAs. Protein bridge and aggregation assays were performed by gel electrophoresis followed by silver staining and band densitometry. Viral replication was evaluated in vitro using epithelial Caco-2 cells. Results indicate that COVID-19 patients (n = 12) show decreased pulmonary levels of SP-D (median = 68.9 ng/mL) when compared to levels reported for healthy controls in literature. Binding assays demonstrate that SP-D binds the SARS-CoV-2 glycosylated spike-(S)-protein of different emerging clinical variants. Binding induces the formation of protein bridges, the critical step of viral aggregation to facilitate its clearance. SP-D inhibits SARS-CoV-2 replication in Caco-2 cells (EC90 = 3.7 µg/mL). Therefore, SP-D recognizes and binds to the spike-(S)-protein of SARS-CoV-2 in vitro, initiates the aggregation, and inhibits viral replication in cells. Combined with the low levels of SP-D observed in COVID-19 patients, these results suggest that SP-D is important in the immune response to SARS-CoV-2 and that rhSP-D supplementation has the potential to be a novel class of anti-viral that will target SARS-CoV-2 infection.