Aetiology of Hospitalized Fever and Risk of Death at Two Rural Tertiary Care Hospitals in Uganda from August 2019 to August 2020 (preprint)

Background: Epidemiology of febrile illness in Uganda is shifting due to increased HIV treatment access, emerging viruses, and increased surveillance. We investigated the aetiology and outcomes of acute febrile illness in adults presenting to hospital using a standardized testing algorithm of available assays in two tertiary care hospitals in Uganda. Methods: We recruited adults with a ≥ 38.0°C temperature or history of fever within 48 hours of presentation. Medical history, demographics, and vital signs were recorded. Testing performed included a complete blood count, renal and liver function, malaria smears, blood culture, and human immunodeficiency virus (HIV). When HIV positive; cryptococcal antigen, CD4 count, and urine lateral flow lipoarabinomannan assay for tuberculosis. Participants were followed during hospitalization and at a 1-month visit. A Cox proportional hazard regression was performed to evaluate for baseline clinical features and risk of death. Results: Of 132 participants, the median age was 33.5 years (IQR 24 to 46) and 58.3% (n=77) were female. Overall, 73 (55.3%) of 132 had a positive microbiologic result. Among those living with HIV, 31 (68.9%) of 45 had at least one positive assay; 16 (35.6%) had malaria, 14 (31.1%) tuberculosis, and 4 (8.9%) cryptococcal antigenemia. The majority (65.9%) were HIV-negative; 42 (48.3%) of 87 had at least one diagnostic assay positive; 24 (27.6%) had positive malaria smears and 1 was Xpert MTB/RIF Ultra positive. Overall, 16 (12.1%) of 132 died; 9 (56.3%) of 16 were HIV-negative, 6 died after discharge. High respiratory rate (≥22 breaths per minute) (hazard ratio [HR] 8.05; 95% CI: 1.81 to 35.69) and low (i.e., <92%) oxygen saturation (HR 4.33; 95% CI: 1.38 to 13.61) were identified to be associated with increased risk of death. Conclusion: In those with hospitalized fever, malaria and tuberculosis were common causes of febrile illness, but most deaths were non-malarial, and most HIV-negative participants did not have a positive diagnostic result. Those with respiratory failure had a high risk of death.

Clinical and experimental factors that affect the reported performance characteristics of rapid testing for SARS-CoV-2 (preprint)

ABSTRACT Tests that detect the presence of SARS-CoV-2 antigen in clinical specimens from the upper respiratory tract can provide a rapid means of COVID-19 disease diagnosis and help identify individuals that may be infectious and should isolate to prevent SARS-CoV-2 transmission. This systematic review assesses the diagnostic accuracy of SARS-CoV-2 antigen detection in COVID-19 symptomatic and asymptomatic individuals compared to RT-qPCR, and summarizes antigen test sensitivity using meta-regression. In total, 83 studies were included that compared SARS-CoV-2 rapid antigen lateral flow testing (RALFT) to RT-qPCR for SARS-CoV-2. Generally, the quality of the evaluated studies was inconsistent, nevertheless, the overall sensitivity for RALFT was determined to be 75.0% (95% confidence interval [CI]: 71.0-78.0). Additionally, RALFT sensitivity was found to be higher for symptomatic versus asymptomatic individuals and was higher for a symptomatic population within 7 days from symptom onset (DSO) compared to a population with extended days of symptoms. Viral load was found to be the most important factor for determining SARS-CoV-2 antigen test sensitivity. Other design factors, such as specimen storage and anatomical collection type, also affect the performance of RAFLT. RALFT and RT-qPCR testing both achieve high sensitivity when compared to SARS-CoV-2 viral culture.

Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection (preprint)

SUMMARY What is already known about this topic? Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period. What is added by this report? We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. What are the implications for public health practice? RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.