Laboratory markers of severity across three COVID-19 outbreaks in Australia: has Omicron and vaccinations changed disease presentation?

COVID-19 has rapidly evolved since it was first discovered in December 2019. We aimed to retrospectively review our experience with COVID-19 infection across 2020-2022, focusing on differences in laboratory markers at presentation. Consecutive adult patients admitted to hospital with confirmed COVID-19 infection were retrospectively reviewed across three periods (29/3/2020-29/9/2020, 16/8/2021-13/10/2021 and 1/1/2022-31/1/2022), correlating with the lineages B.1.338, Delta (B.1.617.2) and Omicron (B.1.1.159), respectively. Laboratory findings of the first requested blood test within 24 h of presentation were recorded and correlated with patient outcome. The primary outcome was requirement for oxygen therapy at any point. Inflammatory markers, namely serum ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) were significantly lower on presentation during 2022 compared to 2021, corresponding to a milder disease course. More than 80% of 2022 patients had received 2 or more vaccine doses and fully vaccinated patients displayed significantly lower inflammatory markers at presentation. Using 2022 data, a multivariate prediction model was constructed to predict for oxygen requirement, with c-statistic 0.86. Patients in 2022, corresponding with the Omicron variant, displayed a milder disease course, even in hospitalised patients, with the majority not requiring oxygen and lower inflammatory markers. We constructed a simple-to-use risk prediction model with c-statistic 0.86 which may identify individuals who can be safely managed as outpatients in the era of highly transmissible variants.

SARS-CoV-2 Testing Strategies in the Diagnosis and Management of COVID-19 Patients in Low-Income Countries: A Scoping Review.

The accuracy of diagnostic laboratory tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can impact downstream clinical procedures in managing and controlling the outbreak of coronavirus disease 2019 (COVID-19). To assess the effectiveness of laboratory tools for managing COVID-19 patients in low-income countries (LICs), we systematically searched the PubMed, Embase, Scopus and CINHAL databases for reports published between January 2020 and June 2022. We found that 22 of 1303 articles reported the performance of various SARS-CoV-2 detection tools across 10 LICs. These tools were (1) real-time reverse transcriptase polymerase chain reaction (RT-PCR); (2) reverse transcription loop-mediated isothermal amplification (RT-LAMP); (3) rapid diagnostic tests (RDTs); (4) enzyme-linked immunosorbent assay (ELISA); and (5) dot-blot immunoassay. The detection of COVID-19 is largely divided into two main streams-direct virus (antigen) detection and serology (immunoglobulin)-based detection. Point-of-care testing using antigen-based RDTs is preferred in LICs because of cost effectiveness and simplicity in the test procedures. The nucleic acid amplification technology (RT-PCR and RT-LAMP) has the highest diagnostic performance among the available tests, but it is not broadly used in this context due to costs and shortage of facilities/trained staff. The serology-based test method is affected by antibody interferences and varying amounts of SARS-CoV-2 immunoglobulins expressed at different stages of disease onset. We further discuss the effectiveness and shortcomings of each of these tools in the diagnosis and management of COVID-19. Using the LICs as the study model, our findings highlight ways to improve the quality and turnaround time of COVID-19 testing in resource-constrained settings, notably through local/international collaborative efforts to refine the molecular-based or immunoassay-based testing technologies.

Impaired Fibrinolytic Potential Predicts Oxygen Requirement in COVID-19.

Abnormal coagulation and fibrinolysis contributes to the respiratory distress syndrome in COVID-19. We aimed to explore the association of impaired fibrinolytic potential with disease severity and oxygen requirement in hospitalized patients. Adults admitted to hospital with confirmed COVID-19 infection between 1-31 January 2022 were included, corresponding to the first Omicron outbreak in Melbourne, Victoria. The first citrated plasma sample requested within 24 h of the patient's presentation was obtained and analyzed by the overall hemostatic potential (OHP) assay, a spectrophotometric assay in which fibrin formation (triggered by small amounts of thrombin (OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP and OFP%)) were simultaneously measured. There were 266 patients (median 72 years, 52.9% male), of which 49.6% did not require oxygen therapy. COVID-19 severity and requirement for oxygen was significantly associated with higher OCP, OHP, and lower OFP%. Vaccinated individuals compared with non-vaccinated individuals had significantly lower OHP (16.5 vs. 23.1, p = 0.015) and higher OFP (72.0% vs. 65.1%, p = 0.005), as well as significantly lower AST, ferritin, LDH, CRP, and D-dimer. A multivariate model containing OHP was constructed with the outcome of oxygen requirement, with c-statistic of 0.85 (95%CI 0.81-0.90). In this pilot study, we show a significant correlation between OHP results and requirement for oxygen supplementation in hospitalized patients during a period dominated by the Omicron variant. The results were incorporated into a multivariate model that predicted for oxygen requirement, with high discriminative ability.

Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease.

Angiotensin converting enzyme 2 (ACE2) is an endogenous negative regulator of the renin-angiotensin system, a key factor in the development of cardiovascular disease (CVD). ACE2 is also used by SARS-CoV-2 for host cell entry. Given that COVID-19 is associated with hypercoagulability, it is timely to explore the potential relationship between plasma ACE2 activity and the coagulation profile. In this cross-sectional study, ACE2 activity and global coagulation assays (GCA) including thromboelastography, thrombin, and fibrin generation were measured in adult healthy controls (n = 123; mean age 41 ± 17 years; 35% male) and in patients with cardiovascular risk factors and/or disease (n = 258; mean age 65 ± 14 years; 55% male). ACE2 activity was significantly lower in controls compared to patients with cardiovascular risk factors and/or disease (median 0.10 (0.02, 3.33) vs. 5.99 (1.95, 10.37) pmol/mL/min, p < 0.001). Of the healthy controls, 48% had undetectable ACE2 activity. Controls with detectable ACE2 had lower maximum amplitude (p < 0.001). In patients with cardiovascular risk factors and/or disease, those in the 3rd tertile were older and male (p = 0.002), with a higher Framingham grade and increased number of cardiovascular risk factors (p < 0.001). In conclusion, plasma ACE2 activity is undetectable to very low in young healthy controls with minimal clinically relevant associations to GCA. Patients with cardiovascular risk factors and/or disease have increased plasma ACE2 activity, suggesting that it may be an important biomarker of endothelial dysfunction and atherosclerosis.

Risk factors and early prediction of clinical deterioration and mortality in adult COVID-19 inpatients: an Australian tertiary hospital experience.

BACKGROUND: Early recognition of severe COVID-19 is essential for timely patient triage. AIMS: To report clinical and laboratory findings and patient outcomes at a tertiary hospital in Melbourne, Australia. METHODS: This is a retrospective study of adult inpatients with COVID-19 admitted to Northern Health from March to September 2020. Data were extracted from electronic medical records. RESULTS: Key admission data were available for 182 patients (median age 67.0 years (interquartile range, 47.9-83.1); 51.1% female). Fifty-six (30.8%) were from residential care. One hundred and seventeen (64.3%) patients were assigned Goals of Patient Care (GOPC) A or B and 65 (35.7%) GOPC C or D. Comorbidities were present in 135 patients (74.2%). 63.2% of patients received antibiotics, 6.6% had antivirals, 45.6% received systemic glucocorticoid and 3.3% had tocilizumab. Fifty-six (30.8%) developed clinical deterioration (24 requiring ventilation, 21 receiving critical care, 34 died). Overall, inhospital clinical deterioration was significantly associated with older age (P < 0.001), history of diabetes (P = 0.038), lower lymphocyte count (P = 0.002) and platelet count (P = 0.004), higher neutrophil-to-lymphocyte ratio (P = 0.002), elevated fibrinogen (P = 0.004), higher serum ferritin (P = 0.027) and C-reactive protein (CRP; P = 0.002). The accuracy of the 4C Deterioration model was moderate, with an area under the curve (AUC) of 0.79 (95% confidence interval (CI), 0.68-0.90) compared with an AUC of 0.77 (95% CI, 0.76-0.78) in the original validation cohort. CONCLUSIONS: In the present study, high neutrophil-to-lymphocyte ratio, abnormal d-dimer, high serum CRP and ferritin appear to be useful prognostic markers.