Recent progress in microfluidic biosensors with different driving forces

Microfluidic biosensors integrating fluid control, target recognition, as well as signal transduction and output, have been widely used in the field of disease diagnosis, drug screening, food safety and environmental monitoring in the past two decades. As the central part and technical characteristics of microfluidic biosensors, the fluid control is not only associated with accuracy and convenience of the sensors, but also affects the material selection and working mode of the sensors. This review summarizes the fluid driving forces for microfluidic biosensors, including gravity, capillary force, centrifugal force, pressure, light, sound, electrical, and magnetic forces. Then, the recent advances in microfluidic biosensors for the detection of viruses, cells, nucleic acids, proteins and small molecules are discussed. Finally, we propose the current challenges and future perspectives of microfluidic biosensors. We hope this review can provide readers with a new perspective to understand the technical characteristics and application potential of microfluidic biosensors.Copyright © 2022 Elsevier B.V.

CD8 T cell immunity after respiratory viral infection is transient, while CD8 T cell immunity after epidermal vaccination is lung focused and durable

Pandemic respiratory viral pathogens like Influenza A and SARS COV2 exhibit continuous and evasive mutations in cell surface molecules, making vaccination with the goal of antibody-mediated protection elusive. CD8 T cells mediate eradication of viral disease, and vaccination to conserved internal viral proteins to elicit CD8 T cell memory is a promising strategy. Using a mouse model, we compared pulmonary infection with H1N1 influenza with skin (epidermal) vaccination using Modified Vaccinia Ankara (MVA) expressing highly conserved NP or another conserved Ags. H1N1 influenza pulmonary infection led to recruitment and lung infiltration with Ag specific CD8 T cells by day 5-10. By day 40, abundant CD8 lung TRM and LN TCM were present. Surprisingly, by day 80, both lung TRM and systemic TCM cells were greatly diminished and were absent at day 120. These mice were protected against lethal challenge at day 40 but not day 80, suggesting built-in obsolescence of CD8 memory. In contrast, epidermal vaccination led to CD8 T cell infiltration of lung at day 5-10, measurable at day 40 and still detectable at day 80 in lung, LN and spleen. In addition, a novel intravascular lung population of CD8 T cells was present at all time points. These mice were completely protected against lethal flu challenge at day 80 and 120. Protection was observed after pulmonary challenge with either H1N1 or H3N2 influenza as well as in B cell depleted mice. We analyzed protective immunity in skin vaccinated mice. At 2 hours after pulmonary challenge, Ag specific CD8 T cells moved from the intravascular space into the lung parenchyma, were abundant at day 3 and persisted for >80 days. Single cell RNA sequencing indicated that these intravascular T cells were transcriptionally distinct from systemic TEM and TCM. We conclude that CD8 T cell immunity after pulmonary infection is powerful but short-lived, while skin vaccine induced CD8 T cell protective immunity is mediated by lung intravascular T cells is protective and durable.

SARS-CoV-2 Remained Airborne for a Prolonged Time in a Lockdown Confined Space

Airborne transmission of COVID-19 plays an important role for the pandemic. However, nucleic acid based evidence of direct association of COVID-19 with environmental contamination is lacking. Here, we investigated a COVID-19 outbreak with two fast food employees infected, in which a traveler despite of a 14-day quarantine turned positive after check in with a hotel, using environmental SARS-CoV-2 sampling, epidemiological tracing, viral RNA sequence as well as surveillance method. Out of 25 positive environmental air and surface swab samples (N = 237) collected, SARS-CoV-2 was found to have remained airborne (5640–7840 RNA copies m–3 ) for more than 4 days in a female washroom. After aging for 5 days in the air, no viable virus was detected. The traveler did not have any contacts with the two employees;however, genome sequencing showed that SARS-CoV-2 variants from three patients and two environmental surface samples belonged to 20B viral clade, sharing a nucleic acid identity of more than 99.9%. We concluded that the outbreak was triggered by SARS-CoV-2 contaminated environments, where the employees inhaled the virus from the air or touching facility surfaces where the traveler did not have any physical contacts with. © The Author(s).

The timing and effectiveness of implementing mild interventions of COVID-19 in large industrial regions via a synthetic control method

The outbreak of novel coronavirus disease (COVID-19) has spread around the world since it was detected in December 2019. The Chinese government executed a series of interventions to curb the pandemic. The "battle" against COVID-19 in Shenzhen, China is valuable because populated industrial cities are the epic centres of COVID-19 in many regions. We made use of synthetic control methods to create a reference population matching specific characteristics of Shenzhen. With both the synthetic and observed data, we introduced an epidemic compartmental model to compare the spread of COVID-19 between Shenzhen and its counterpart regions in the United States that didn't implement interventions for policy evaluation. Once the effects of policy interventions adopted in Shenzhen were estimated, the delay effects of those interventions were referred to provide the further control degree of interventions. Thus, the hypothetical epidemic situations in Shenzhen were inferred by using time-varying reproduction numbers in the proposed SIHR (Susceptible, Infectious, Hospitalized, Removed) model and considering if the interventions were delayed by 0 day to 5 days. The expected cumulative confirmed cases would be 1546, which is 5.75 times of the observed cumulative confirmed cases of 269 in Shenzhen on February 3, 2020, based on the data from the counterpart counties (mainly from Broward, New York, Santa Clara, Pinellas, and Westchester) in the United States. If the interventions were delayed by 5 days from the day when the interventions started, the expected cumulative confirmed cases of COVID-19 in Shenzhen on February 3, 2020 would be 676 with 95% credible interval (303,1959). Early implementation of mild interventions can subdue the epidemic of COVID-19. The later the interventions were implemented, the more severe the epidemic was in the hard-hit areas. Mild interventions are less damaging to the society but can be effective when implemented early.

[COVID-19 epidemic and its characteristics in Heilongjiang province].

Objective: To describe the COVID-19 epidemic and its characteristics in Heilongjiang province, and provide evidence for the further prevention and control of COVID-19 in the province. Methods: The information of COVID-19 cases and clusters were collected from national notifiable disease report system and management information system for reporting public health emergencies of China CDC. The Software's of Excel 2010 and SPSS 23.0 were applied for data cleaning and statistical analysis on the population, time and area distributions of COVID-19 cases. Results: On January 22, 2020, the first confirmed case of COVID-19 was reported in Heilongjiang. By March 11, 2020, a total of 482 cases domestic case of COVID-19, The incidence rate was 1.28/100 000, the mortality rate was 2.70% (13/482) in 13 municipalities in Heilongjiang. There were 81 clusters of COVID-19, The number of confirmed cases accounted for 79.25% (382/482) of the total confirmed cases and 12 cases of deaths. The family clusters accounted for 86.42% (70/81). Compared with the sporadic cases, the mortality rate, proportion of elderly cases aged 60 or above and severe or critical cases of clinical classification were all higher in the clusters especially the family clusters, but the differences were not significant (P>0.05). There were 34 clusters involving more than 5 confirmed cases accounted for 41.98% (34/81) of the total clusters, the involved cases accounted for 68.31% (261/382) of the total cases of clusters. There were significant differences in age distribution of the cases among the case clusters with different case numbers. In the clusters involving 6-9 cases, the proportion of cases aged 65 years or above was more (26.53%, 39/147). Conclusions: The incidence rate of COVID-19 was relatively high and the early epidemic was serious in Heilongjiang, The number of cases was large in clusters especially family clusters.

The relationship between lymphocyte recovery, specific antibody level and 2019-nCoV reversion in convalescent patients with COVID-19

Objective: A retrospective analysis was performed on COVID-19 patients to explore the correlations among lymphocytes, virus-specific antibodies (immunoglobulin M and immunoglobulin G) and the 2019 novel coronavirus (2019-nCoV) reversion. Methods: A total of 69 patients diagnosed with COVID-19 in Lu'an Hospital affiliated to Anhui Medical University from January 20, 2020 to March 3, 2020 were recruited. Throat swab specimens were collected and tested by real-time polymerase chain reaction for 2019-nCoV in 14 days post-discharge. Seven patients (mean age 36.3±5.8 years) experienced virus reversion were selected as reversion group, while the 62 remaining cases (mean age 44.4±11.5 years) were assigned to the recovery group. The parametric/non-parametric tests were applied to discriminate clinical features and total lymphocyte count (on admission and on discharge) between the two groups. One-way ANOVA was used to evaluate the impact of lymphocyte on different stages of disease course in virus-reversion group. Specific antibody levels were compared by using nonparametric tests. Results: Virus reversion occurred at a rate of 10% (7/69). The reversion period took a median 8 days. There was no significant difference between the two groups in length of hospital stay, age, gender, history of smoking and/or drinking, coinfection and underlying disease (P>0.05). Total lymphocyte count in recovery group was significantly higher on discharge than on admission [(1.29±0.33)×109/L, (1.14±0.41)×109/L, respectively;t=-2.097, P=0.038], while there were no significant change in reactivation group [(1.48±0.51)×109/L, (1.54±0.74)×109/L, respectively;t=0.206, P=0.840]. Total lymphocyte count was significantly higher in reversion group than in recover group both on admission and at discharge (t=-2.552, P=0.016;t=-2.023, P=0.048). No apparent change was found in total lymphocyte count during the different stage of disease in reversion group [(1.54±0.74)×109/L, (1.48±0.51)×109/L, (1.64±0.33)×109/L, (1.57±0.31)×109/L, respectively;F=0.127, P=0.943]. There was no significant difference in levels of IgM [2.65(1.98, 3.45), 2.95(1.31, 4.51)], and IgG [4.61(4.01, 5.78), 4.56(2.50, 5.45)between the two groups (Z=-0.295, P=0.768;Z=-0.319, P=0.075), respectively. Conclusion: The immune systems of COVID-19 patients at high risk for virus reversion may respond lightly to the 2019-nCOV infection, leading to a prolonged virus presence after discharge.