Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers. The future of public health is likely to become increasingly digital, and we review the need for the alignment of international strategies for the regulation, evaluation and use of digital technologies to strengthen pandemic management, and future preparedness for COVID-19 and other infectious diseases. Public-health need Digital tool or technology Example of use Refs. Digital epidemiological surveillance Machine learning Web-based epidemic intelligence tools and online syndromic surveillance Web-based epidemic intelligence tools: 20-23,25 Based on social media or online search data: 30-33 Survey apps and websites Symptom reporting 37,38,48,49 Data extraction and visualization Data dashboard 39-45 Rapid case identification Connected diagnostic device Point-of-care diagnosis 58 Sensors including wearables Febrile symptoms checking 51-53 Machine learning Medical image analysis 65,66

Paper-based lateral flow immunoassays (LFIAs) are one of the most widely used point-of-care (PoC) devices; however, their application in early disease diagnostics is often limited due to insufficient sensitivity for the requisite sample sizes and the short time frames of PoC testing. To address this, we developed a serum-stable, nanoparticle catalyst-labeled LFIA with a sensitivity surpassing that of both current commercial and published sensitivities for paper-based detection of p24, one of the earliest and most conserved biomarkers of HIV. We report the synthesis and characterization of porous platinum core–shell nanocatalysts (PtNCs), which show high catalytic activity when exposed to complex human blood serum samples. We explored the application of antibody-functionalized PtNCs with strategically and orthogonally modified nanobodies with high affinity and specificity toward p24 and established the key larger nanoparticle size regimes needed for efficient amplification and performance in LFIA. Harnessing the catalytic amplification of PtNCs enabled naked-eye detection of p24 spiked into sera in the low femtomolar range (ca. 0.8 pg·mL–1) and the detection of acute-phase HIV in clinical human plasma samples in under 20 min. This provides a versatile absorbance-based and rapid LFIA with sensitivity capable of significantly reducing the HIV acute phase detection window. This diagnostic may be readily adapted for detection of other biomolecules as an ultrasensitive screening tool for infectious and noncommunicable diseases and can be capitalized upon in PoC settings for early disease detection.

The quantum spin properties of nitrogen-vacancy defects in diamond have diverse applications including quantum computing and communications 1 , but nanodiamonds also have attractive properties for in vitro biosensing, including brightness 2 , low cost 3 , and selective manipulation of their emission 4 . Nanoparticle-based biosensors are vital for early disease detection, however, often lack the required sensitivity. Here we investigated fluorescent nanodiamonds as an ultra-sensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity 5 , and frequency-domain analysis 6 to separate the signal from background autofluorescence 7 , which typically limits sensitivity.We focused on the common, low-cost lateral flow format as an exemplar, achieving detection limits of 8.2 × 10 −19 M for a biotin-avidin model, 10 5 -fold more sensitive than gold nanoparticles; and a use-case demonstration of single-copy detection of HIV-1 RNA with a short 10-minute isothermal amplification step, including a pilot using a clinical plasma sample with an extraction step. This ultra-sensitive quantum-diagnostics platform is applicable to numerous diagnostic test formats and diseases with the potential to transform early diagnosis, benefiting patients and populations.Rapid point-of-care tests have transformed access to disease testing in a variety of community settings, including clinics, pharmacies and the home 30 . Among the most common tests worldwide are paper microfluidic lateral flow assays (LFAs), with 276 million sold in 2017 for malaria alone 31 . LFAs satisfy many of the REASSURED criteria 32 for diagnostics, however, despite widespread use they are still limited by inadequate sensitivity to detect the low levels of biomarkers necessary for early disease detection.Fluorescent markers can be highly sensitive, but are practically limited by background fluorescence from the sample, substrate, or readout technique. In the case of nitrocellulose substrates used in LFAs, there is a significant background autofluorescence 7 , which inherently limits sensitivity. Various methods have been reported to reduce this effect, such as membrane modification to reduce background fluorescence 33 , exciting in the nearinfrared range and using upconverting nanoparticles 34 , and time-gated detection using longpersistent phosphors 35 to separate background fluorescence, which has a shorter lifetime.These methods have shown ∼10-fold improvements in sensitivity over gold nanoparticles, limited by relatively low brightness.Here we show the use of FNDs as a fluorescent label in an LFA format as a demonstrator of their first use for in vitro diagnostics, taking advantage of their high brightness and selective modulation. The use of a narrowband resonator allows for the lowpower generation of microwave-frequency electromagnetic fields, suitable for a point-ofcare device, to efficiently separate the signal from the background in the frequency domain by lock-in 6 detection. We aimed, after characterisation, functionalisation,...