Heterogeneous influence of individuals' behavior on mask efficacy in gathering environments

Wearing masks is an easy way to operate and popular measure for preventing epidemics. Although masks can slow down the spread of viruses, their efficacy in gathering environments involving heterogeneous person-to-person contacts remains unknown. Therefore, we aim to investigate the epidemic prevention effect of masks in different real-life gathering environments. This study uses four real interpersonal contact datasets to construct four empirical networks to represent four gathering environments. The transmission of COVID-19 is simulated using the Monte Carlo simulation method. The heterogeneity of individuals can cause mask efficacy in a specific gathering environment to be different from the baseline efficacy in general society. Furthermore, the heterogeneity of gathering environments causes the epidemic prevention effect of masks to differ. Wearing masks can greatly reduce the probability of clustered epidemics and the infection scale in primary schools, high schools, and hospitals. However, the use of masks alone in primary schools and hospitals cannot control outbreaks. In high schools with social distancing between classes and in workplaces where the interpersonal contact is relatively sparse, masks can meet the need for prevention. Given the heterogeneity of individual behavior, if individuals who are more active in terms of interpersonal contact are prioritized for mask-wearing, the epidemic prevention effect of masks can be improved. Finally, asymptomatic infection has varying effects on the prevention effect of masks in different environments. The effect can be weakened or eliminated by increasing the usage rate of masks in high schools and workplaces. However, the effect on primary schools and hospitals cannot be weakened. This study contributes to the accurate evaluation of mask efficacy in various gathering environments to provide scientific guidance for epidemic prevention. © 2022, Higher Education Press.

Forecasting the impact of epidemic outbreaks on the supply chain: modelling asymptomatic cases of the COVID-19 pandemic

An epidemic outbreak largely disrupts supply chains (SCs) worldwide through plummeting business confidence, especially when it becomes a pandemic;its unpredictable re-emergence and spreadability may lead to inappropriate decision-making, in turn causing severe economic shocks. In March 2020, the coronavirus disease 2019 (COVID-19) outbreak attained a pandemic level, and many millions of cases were confirmed globally. Many countries reported an increasing number of active cases and formulated long-term lockdown guidelines, which resulted in an unexpected disruption of SCs. A key challenge in this scenario is that the rising number of confirmed COVID-19 cases does not necessarily reflect the already infected or asymptomatic cases. It is thus critical to understand the impact of asymptomatic carriers on the SC, as they may be the key driver of the novel virus spread, disrupting long-term SCs. This paper generalised the susceptible-exposed-infected-recovered (S-E-I-R) approach to create a mathematical model for which the impact of a proposed asymptomatic situation on the SC is evaluated through the basic reproduction number (R0), considered the main driver of SC disruption and the equilibrium status of infection over time. This paper presents an action plan for reducing disruption in the SC based on the R0 of the model. Overall, the current study as validated through a case study suggests that the asymptomatic-situation-based model is more convenient for critically understanding as well as forecasting the outbreak's impact on SCs. This study also highlights different perspectives of SCs for managing such types of pandemics using modelling approaches.

Dynamics of disease characteristics and viral RNA decay in patients with asymptomatic and mild infections during the Omicron wave in Shanghai, China: A retrospective cohort study.

OBJECTIVES: Asymptomatic infections and mild diseases were more common during the Omicron outbreak in Shanghai, China in 2022. This study aimed to assess the characteristics and viral RNA decay between patients with asymptomatic and mild infections. METHODS: A total of 55,111 patients infected with SARS-CoV-2 who were quarantined in the National Exhibition & Convention Center (Shanghai) Fangcang shelter hospital within 3 days after diagnosis from April 9 to May 23, 2022 were enrolled. The kinetics of cycle threshold (Ct) values of reverse transcription-polymerase chain reaction were assessed. The influencing factors for disease progression and the risk factors for the viral RNA shedding time (VST) were investigated. RESULTS: On admission, 79.6% (43,852/55,111) of the cases were diagnosed with asymptomatic infections, and 20.4% were mild diseases. However, 78.0% of initially asymptomatic subjects developed mild diseases at the follow-up. The final proportion of asymptomatic infections was 17.5%. The median time of symptom onset, the duration of symptoms, and the VST were 2 days, 5 days, and 7 days, respectively. Female, age 19-40 years, underlying comorbidities with hypertension and diabetes, and vaccination were associated with higher risks of progressing to mildly symptomatic infections. In addition, mildly symptomatic infections were found to be associated with prolonged VST compared with asymptomatic infections. However, the kinetics of viral RNA decay and dynamics of Ct values were similar among asymptomatic subjects, patients with asymptomatic-to-mild infection, and patients with mild infection. CONCLUSION: A large proportion of initially diagnosed asymptomatic Omicron infections is in the presymptomatic stage. The Omicron infection has a much shorter incubation period and VST than previous variants. The infectivity of asymptomatic infections and mildly symptomatic infections with Omicron is similar.

Immune cell landscape in symptomatic and asymptomatic SARS-CoV-2 infected adults and children in urban Dhaka, Bangladesh.

OBJECTIVES: The study of cellular immunity to SARS-CoV-2 is crucial for evaluating the course of the COVID-19 disease and for improving vaccine development. We aimed to assess the phenotypic landscape of circulating lymphocytes and mononuclear cells in adults and children who were seropositive to SARS-CoV-2 in the past 6 months. METHODS: Blood samples (n = 350) were collected in a cross-sectional study in Dhaka, Bangladesh (Oct 2020-Feb 2021). Plasma antibody responses to SARS-CoV-2 were determined by an electrochemiluminescence immunoassay while lymphocyte and monocyte responses were assessed using flow cytometry including dimensionality reduction and clustering algorithms. RESULTS: SARS-CoV-2 seropositivity was observed in 52% of adults (18-65 years) and 56% of children (10-17 years). Seropositivity was associated with reduced CD3+T cells in both adults (beta(ß) = -2.86; 95% Confidence Interval (CI) = -5.98, 0.27) and children (ß = -8.78; 95% CI = -13.8, -3.78). The frequencies of T helper effector (CD4+TEFF) and effector memory cells (CD4+TEM) were increased in seropositive compared to seronegative children. In adults, seropositivity was associated with an elevated proportion of cytotoxic T central memory cells (CD8+TCM). Overall, diverse manifestations of immune cell dysregulations were more prominent in seropositive children compared to adults, who previously had COVID-like symptoms. These changes involved reduced frequencies of CD4+TEFF cells and CD163+CD64+ classical monocytes, but increased levels of intermediate or non-classical monocytes, as well as CD8+TEM cells in symptomatic children. CONCLUSION: Seropositive individuals in convalescence showed increased central and effector memory T cell phenotypes and pro-resolving/healing monocyte phenotypes compared to seronegative subjects. However, seropositive children with a previous history of COVID-like symptoms, displayed an ongoing innate inflammatory trait.

Vaccination, symptomatic infection and negative conversion of viral RNA by body mass index, diabetes, and age: An observational study.

BACKGROUND: The associations of doses of vaccine received with symptomatic infection with SARS-CoV-2 and negative conversion rate of viral RNA by BMI, diabetes, and age are unclear. METHODS: Included were adult cases of SARS-CoV-2 infection hospitalized at a makeshift hospital in Shanghai (N = 38,592). Each case received a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test every day until discharge. Symptomatic cases had ≥1 pre-specified symptoms. Negative conversion time (NCT) was the duration between the specimen collection date associated with the first positive RT-PCR test and the first test date of the two consecutive negative tests at least 24 h apart. BMI-, diabetes- and age-stratified multivariable logistic and Poisson regressions were applied. FINDINGS: Coexistence of overweight/obesity and diabetes was associated with a higher risk of symptomatic infection and a longer NCT compared with coexistence of normal weight and without diabetes, but this association was primarily attributed to underlying comorbidities. Compared with absence of vaccination, booster vaccination, but not full vaccination, was consistently associated with a 42 %-56 % lower odds of symptomatic infection and ∼1.6-1.8 days of shorter NCT across different strata separately for weight and diabetes. Age-stratified analyses found that the effectiveness of booster vaccination did not attenuate with age, except for preventing symptomatic infection among adults with diabetes. INTERPRETATION: BMI and diabetes co-determined their associations with symptomatic infection and NCT. Booster vaccination but not full vaccination was associated a lower risk of symptomatic infection, a shorter NCT or both regardless of BMI, diabetes status and age.

COVID-19 infection, and reinfection, and vaccine effectiveness against symptomatic infection among health care workers in the setting of omicron variant transmission in New Delhi, India.

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022. Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-. Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed. Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination. Funding: None.

A Comparative Analysis of COVID-19 IgG Antibody Level and Socio-Demographic Status in Symptomatic and Asymptomatic Population of South Andaman, India.

INTRODUCTION: The serosurveillance of COVID-19 antibody levels and their difference between symptomatic and asymptomatic groups can help in understanding the immune status of the community and the factors affecting it. Hence, the study was undertaken to find the differences between these two groups with respect to antibodies level and other socio-demographic variables in the South Andaman district. METHODS: A population-based serosurveillance study covering more than 4,000 samples was carried out in the South Andaman district. The participants were selected by multistage cluster sampling. The venous blood samples were tested for IgG COVID-19 antibodies by Erba Lisa Elisa kit. RESULTS: 5.3% of total individuals (217) were symptomatic whereas 94.7% (3,872) were asymptomatic. The symptomatic individuals had lower antibodies (33.6%) as compared to asymptomatic individuals (40.1%) (p-value=0.059). In the age group of 31-45 years, antibody positivity in the asymptomatic group was significantly higher than in the symptomatic group (p-value 0.031). The antibody positivity was higher in moderate to severe cases who needed hospital admission. The antibody positivity was found similar in both the groups in front-line workers as well as in non-front-line workers (p-value=0.104, 0.274, respectively). CONCLUSION: The antibody positivity was higher in asymptomatic individuals as compared to symptomatic individuals, particularly in the age group of 31-45 years. The higher level of antibody positivity in asymptomatic individuals reflected a stronger immune response which led to no clinical manifestations. The antibody positivity was also found higher in moderate to severe cases undergoing hospital admission whereas antibodies positivity was found similar in front-line and non-front-line workers.

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology.

Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.

Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates.

BACKGROUND: Pregnant women and their neonates represent 2 vulnerable populations with an interdependent immune system that are highly susceptible to viral infections. The immune response of pregnant women to severe acute respiratory syndrome coronavirus 2 and the interplay of how the maternal immune response affects the neonatal passive immunity have not been studied systematically. OBJECTIVE: We characterized the serologic response in pregnant women and studied how this serologic response correlates with the maternal clinical presentation and with the rate and level of passive immunity that the neonate received from the mother. STUDY DESIGN: Women who gave birth and who tested positive for immunoglobulin M or immunoglobulin G against severe acute respiratory syndrome coronavirus 2 using semiquantitative detection in a New York City hospital between March 22, 2020, and May 31, 2020, were included in this study. A retrospective chart review of the cases that met the inclusion criteria was conducted to determine the presence of coronavirus disease 2019 symptoms and the use of oxygen support. Serology levels were compared between the symptomatic and asymptomatic patients using a Welch 2 sample t test. Further chart review of the same patient cohort was conducted to identify the dates of self-reported onset of coronavirus disease 2019 symptoms and the timing of the peak immunoglobulin M and immunoglobulin G antibody levels after symptom onset was visualized using local polynomial regression smoothing on log2-scaled serologic values. To study the neonatal serology response, umbilical cord blood samples of the neonates born to the subset of serology positive pregnant women were tested for serologic antibody responses. The maternal antibody levels of serology positive vs the maternal antibody levels of serology negative neonates were compared using the Welch 2 sample t test. The relationship between the quantitative maternal and quantitative neonatal serologic data was studied using a Pearson correlation and linear regression. A multiple linear regression analysis was conducted using maternal symptoms, maternal serology levels, and maternal use of oxygen support to determine the predictors of neonatal immunoglobulin G levels. RESULTS: A total of 88 serology positive pregnant women were included in this study. The antibody levels were higher in symptomatic pregnant women than in asymptomatic pregnant women. Serology studies in 34 women with symptom onset data revealed that the maternal immunoglobulin M and immunoglobulin G levels peak around 15 and 30 days after the onset of coronavirus disease 2019 symptoms, respectively. Furthermore, studies of 50 neonates born to this subset of serology positive women showed that passive immunity in the form of immunoglobulin G is conferred in 78% of all neonates. The presence of passive immunity is dependent on the maternal antibody levels, and the levels of neonatal immunoglobulin G correlate with maternal immunoglobulin G levels. The maternal immunoglobulin G levels and maternal use of oxygen support were predictive of the neonatal immunoglobulin G levels. CONCLUSION: We demonstrated that maternal serologies correlate with symptomatic maternal infection, and higher levels of maternal antibodies are associated with passive neonatal immunity. The maternal immunoglobulin G levels and maternal use of oxygen support, a marker of disease severity, predicted the neonatal immunoglobulin G levels. These data will further guide the screening for this uniquely linked population of mothers and their neonates and can aid in developing maternal vaccination strategies.

The unique features of SARS-CoV-2 transmission: Comparison with SARS-CoV, MERS-CoV and 2009 H1N1 pandemic influenza virus.

From 2002 to 2019, three deadly human coronaviruses (hCoVs), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged to produce outbreaks of SARS, MERS and coronavirus disease 2019 (Covid-19), respectively. All three hCoVs are members of the Betacoronavirus genus in the subfamily Orthocoronavirinae and share many similarities in virology and epidemiology. However, the pattern and scale of Covid-19 global spread is similar to 2009 pandemic H1N1 influenza (H1N1pdm09), rather than SARS or MERS. Covid-19 exhibits high viral shedding in the upper respiratory tract at an early stage of infection, and has a high proportion of transmission competent individuals that are pre-symptomatic, asymptomatic and mildly symptomatic, characteristics seen in H1N1pdm09 but not in SARS or MERS. These two traits of Covid-19 and H1N1pdm09 result in reduced efficiency in identification of transmission sources by symptomatic screening and play important roles in their ability to spread unchecked to cause pandemics. To overcome these attributes of Covid-19 in community transmission, identifying the transmission source by testing for virus shedding and interrupting chains of transmission by social distancing and public masking are required.

Convalescent plasma treatment for SARS-CoV-2 infection: analysis of the first 436 donors in England, 22 April to 12 May 2020.

Serological reactivity was analysed in plasma from 436 individuals with a history of disease compatible with COVID-19, including 256 who had been laboratory-confirmed with SARS-CoV-2 infection. Over 99% of laboratory-confirmed cases developed a measurable antibody response (254/256) and 88% harboured neutralising antibodies (226/256). Antibody levels declined over 3 months following diagnosis, emphasising the importance of the timing of convalescent plasma collections. Binding antibody measurements can inform selection of convalescent plasma donors with high neutralising antibody levels.