Development of a Mobile Health Application Based on a Mixed Prenatal Care in the Context of COVID-19 Pandemic.

OBJECTIVE: We describe the development and structure of a novel mobile application in a mixed model of prenatal care, in the context of the COVID-19 pandemic. Furthermore, we assess the acceptability of this mobile app in a cohort of patients. METHODS: First, we introduced a mixed model of prenatal care; second, we developed a comprehensive, computer-based clinical record to support our system. Lastly, we built a novel mobile app as a tool for prenatal care. We used Flutter Software version 2.2 to build the app for Android and iOS smartphones. A cross-sectional study was carried out to assess the acceptability of the app. RESULTS: A mobile app was also built with the main attribute of being connected in real-time with the computer-based clinical records. The app screens detail information about activities programmed and developed in the prenatal care according to gestational age. A downloadable maternity book is available and some screens show warning signs and symptoms of pregnancy. The acceptability assessment was mostly rated positively regarding the characteristics of the mobile app, by 50 patients. CONCLUSION: This novel mobile app was developed as a tool among pregnant patients to increase the information available about their pregnancies in the provision of a mixed model of prenatal care in the context of the COVID-19 pandemic. It was fully customized to the needs of our users following the local protocols. The introduction of this novel mobile app was highly accepted by the patients.

Rapidly accelerated development of neutralizing COVID-19 antibodies by reducing cell line and CMC development timelines.

Since the Coronavirus Disease 2019 (COVID-19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much-shortened timeline of 3-6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS-CoV-2-neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization  approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late-stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next-generation sequencing-based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID-19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic-related biologics development may innovate typical biologics development timelines and become a new standard in the industry.

The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.

Maternal Perinatal Telemonitoring in the Context of the Coronavirus Disease 2019 Pandemic in a Tertiary Health Center in Peru.

OBJECTIVE: This study aimed to describe the characteristics of a telemonitoring program that was rapidly implemented in our institution as a response to the coronavirus disease 2019 (COVID-19) pandemic, as well as the maternal and perinatal outcomes of women who attended this program. STUDY: DESIGN: Retrospective study of patients via phone-call telemonitoring during the peak period of the COVID-19 pandemic (May 2020-August 2020). Maternal and perinatal outcomes were collected and described. Health providers' satisfaction with the telemonitoring program was assessed via an email survey. RESULTS: Twenty-three (69.7%) health providers answered the survey. The mean age was 64.5 years, 91.3% were OB/GYN (obstetrician-gynecologist) doctors, and 95% agreed that telemonitoring is an adequate method to provide health care when in-person visits are difficult. The 78.7% of scheduled telemonitoring consultations were finally completed. We performed 2,181 telemonitoring consultations for 616 pregnant women and 544 telemonitoring consultations for puerperal women. Other medical specialties offering telemonitoring included gynecology, reproductive health, family planning, cardiology, endocrinology, and following up with patients with reactive serology to severe respiratory syndrome coronavirus 2 (SARS-CoV-2). The majority of the population attending our telemonitoring program were categorized as the lowest strata, i.e., III and IV, according to the Human Development Index, and approximately 42% were deemed as high-risk pregnant women. Additionally, we reported the perinatal outcomes of 424 (63%) pregnant women, the most relevant finding being that approximately 53% of them had cesarean sections. CONCLUSION: Telemonitoring is an adequate method of continuing the provision of prenatal care when in-person visits are difficult in situations such as the COVID-19 pandemic. Telemonitoring is feasible even in institutions with no or little experience in telemedicine. The perinatal outcomes in women with telemonitoring seem to be similar to that in the general population. KEY POINTS: · Telemonitoring for prenatal care is feasible even in low-income countries and in a critical scenario.. · OB/GYN doctors agreed with that telemonitoring is an adequate method to provide prenatal care.. · Maternal and perinatal outcomes are similar in women attending a telemonitoring program..

Three SARS-CoV-2 antibodies provide broad and synergistic neutralization against variants of concern, including Omicron.

The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel of human nAbs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients show diverse neutralization against Omicron, of which XMA01 and XMA04 maintain nanomolar affinities and excellent neutralization (half maximal inhibitory concentration [IC50]: ∼20 ng/mL). nAb XMA09 shows weak but unattenuated neutralization against all variants of concern (VOCs) as well as SARS-CoV. Structural analysis reveals that the above three antibodies could synergistically bind to the receptor-binding domains (RBDs) of both wild-type and Omicron spikes and defines the critical determinants for nAb-mediated broad neutralizations. Three nAbs confer synergistic neutralization against Omicron, resulting from the inter-antibody interaction between XMA04 and XMA01(or XMA09). Furthermore, the XMA01/XMA04 cocktail provides synergistic protection against Beta and Omicron variant infections in hamsters. In summary, our results provide insights for the rational design of antibody cocktail therapeutics or universal vaccines against Omicron.

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants

Zhang et al. show in vitro cross-species infectivity and neutralization-escape characteristics of 153 SARS-CoV-2 RBD mutants and 11 globally circulating VOC/VOI variants. They reveal an association between enhanced cross-species infection potential and the current cumulative prevalence of mutations, which can inform surveillance and forecasting of SARS-CoV-2 spike mutations.

Antiviral/antibacterial biodegradable cellulose nonwovens as environmentally friendly and bioprotective materials with potential to minimize microplastic pollution.

Personal protective equipment (PPE) such as face masks is vital in battling the COVID-19 crisis, but the dominant polypropylene-based PPE are lack of antiviral/antibacterial activities and environmental friendliness, and have hazardous impact on the soil and aquatic ecosystems. The work presented herein focused on developing biodegradable, antiviral, and antibacterial cellulose nonwovens (AVAB-CNWs) as a multi-functional bioprotective layer for better protection against coronavirus SARS-CoV-2 and addressing environmental concerns raised by the piling of COVID-19 related wastes. Both guanidine-based polymer and neomycin sulfate (NEO) were reactive-modified and covalently grafted onto the surface of cellulose nonwovens, thereby conferring outstanding antiviral and antibacterial activities to the nonwovens without deteriorating the microstructure and biodegradability. Through adjusting the grafting amount of active components and selecting appropriate reagents for pretreatment, the antimicrobial activity and hydrophobicity for self-cleaning of the nonwovens can be tuned. More importantly, we demonstrated for the first time that such multi-functional nonwovens are capable of inactivating SARS-CoV-2 instantly, leading to high virucidal activity (> 99.35%), which is unachievable by conventional masks used nowadays. Meanwhile, the robust breathability and biodegradability of AVAB-CNWs were well maintained. The applications of the as-prepared nonwovens as high-performance textile can be readily extended to other areas in the fight against COVID-19.

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist circulating variants.

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.

Functionalized Masks: Powerful Materials against COVID-19 and Future Pandemics.

The outbreak of COVID-19 revealed the vulnerability of commercially available face masks. Without having antibacterial/antiviral activities, the current masks act only as filtering materials of the aerosols containing microorganisms. Meanwhile, in surgical masks, the viral and bacterial filtration highly depends on the electrostatic charges of masks. These electrostatic charges disappear after 8 h, which leads to a significant decline in filtration efficiency. Therefore, to enhance the masks' protection performance, fabrication of innovative masks with more advanced functions is in urgent demand. This review summarizes the various functionalizing agents which can endow four important functions in the masks including i) boosting the antimicrobial and self-disinfectant characteristics via incorporating metal nanoparticles or photosensitizers, ii) increasing the self-cleaning by inserting superhydrophobic materials such as graphenes and alkyl silanes, iii) creating photo/electrothermal properties by forming graphene and metal thin films within the masks, and iv) incorporating triboelectric nanogenerators among the friction layers of masks to stabilize the electrostatic charges and facilitating the recharging of masks. The strategies for creating these properties toward the functionalized masks are discussed in detail. The effectiveness and limitation of each method in generating the desired properties are well-explained along with addressing the prospects for the future development of masks.

Difference in Risk Factors Associated with Acute Respiratory Distress Syndrome and Intubation/Death in Patients with Coronavirus Disease 2019: A Two-hospital Retrospective Cohort Study in Hubei, China (preprint)

Background: The reviews on the risk factors with ARDS and the worse outcomes concluded lacking robust data of risk factors to prevent COVID-19 and identified an urgent need for large sample and high-quality research in this area, as well as the features of the ARDS.Methods: This retrospective cohort study included 333 COVID-19 inpatients at two hospitals in Hubei of China in 2020. The COVID-19-related ARDS was diagnosed according to the Berlin criteria. The outcomes were ARDS development and the intubation or in-hospital death. The cox proportional hazard ratio (HR) models were employed to determine the significant risk factors. Results: The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The survival patients on invasive mechanical ventilation (IMV) had been intubated earlier since ARDS diagnosis than those who had not survived (5.5 median days, IQR 4.0-7.0 days versus 11.5 median days, IQR 6.0-14.0 days, P < 0.001). Males and all abnormal laboratory indices associated with the higher risk of ARDS (P<0.05) but were not linked with the risk of intubation or death (P>0.05). The sensitivity analyses found that lymphocyte count of < 1000 per mm3 at hospital admission were still significantly associated with developing ARDS when adjusting for age and male gender (HR, 4.10; 95% CI, 2.40-7.10), and oxygenation index (OI) ratio < 150 were more likely to predict the intubation/death after age adjustment (HR, 2.50; 95% CI, 1.17-5.30). Conclusion: The SARS-CoV-2-caused ARDS was not the typical ARDS according to Berlin criteria. The alive patients with IMV had been intubated earlier since ARDS diagnosis than those who had not survived. We identified male gender and abnormal laboratory indices associated with the ARDS but were not linked with the intubation/death. Sensitivity analysis concluded lymphocyte count of < 1000 per mm3 could predict ARDS while OI ratio less than 150 could predict intubation/death.

Follow-Up Study of the Chest CT Characteristics of COVID-19 Survivors Seven Months After Recovery.

Background: It has remained a concern whether any long-term pulmonary sequelae exist for COVID-19 survivors. Methods: Forty-one patients (22 men and 19 women, 50 ± 14 years) confirmed with COVID-19 performed follow-up chest CT and cardiopulmonary exercise testing at 7 months after discharge. Patients were divided into fibrosis group and non-fibrosis group according to the evidence of fibrosis on follow-up CT. The clinical data and the CT findings were recorded and analyzed. Results: The predominant CT patterns of abnormalities observed at 7 months after discharge were parenchymal band (41%), interlobular septal thickening (32%), and traction bronchiectasis (29%). Sixty-one percent of the patients achieved complete radiological resolution, and 29% of patients developed pulmonary fibrosis. Compared with the patients in the non-fibrosis group, the patients in the fibrosis group were older, with a longer hospital stay, a higher rate of steroid and mechanical ventilation therapy, lower levels of lymphocyte and T cell count, higher levels of D-dimer and lactic dehydrogenase, and higher quantitative CT parameters (opacity score, volume of opacity, and percentage of opacity) at discharge. Besides, oxygen consumption and metabolic equations were decreased and ventilatory equivalent for carbon dioxide was increased in patients in the fibrosis group. Logistic regression analyses revealed that age, steroid therapy, presence of traction bronchiectasis on chest CT at discharge, and opacity score at discharge, were independent risk factors for developing pulmonary fibrosis at 7 months after discharge. Receiver operating characteristic analysis revealed that the combined clinical-radiological model was better than the clinical-only model in the prediction of pulmonary fibrosis. Conclusions: The chest CT lesions could be absorbed without any sequelae for most patients with COVID-19, whereas older patients with severe conditions are more prone to develop fibrosis, which may further lead to cardiopulmonary insufficiency. The combined clinical-radiological model may predict the formation of pulmonary fibrosis early.

Nucleic acid detection results analysis in different COVID-19 samples

Objective: To understand the results and influencing factors of SARS-CoV-2 nucleic acid detection among specimens in different types and stages of coronavirus disease 2019 (COVID-19) progression.

Neutralizing antibodies against SARS-CoV-2: current understanding, challenge and perspective.

The rapid emergence of Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) as a pandemic that presents an urgent human health crisis. Many SARS-CoV-2 neutralizing antibodies (NAbs) were developed with efficient therapeutic potential. NAbs-based therapeutics against SARS-CoV-2 are being expedited to preclinical and clinical studies with two antibody drugs, LY3819253 (LY-CoV555) and REGN-COV2 (REGN10933 and REGN10987), approved by the US Food and Drug Administration for emergency use authorization for treating COVID-19. In this review, we provide a systemic overview of SARS-CoV-2 specific or cross-reactive NAbs and discuss their structures, functions and neutralization mechanisms. We provide insight into how these NAbs specific recognize the spike protein of SARS-CoV-2 or cross-react to other CoVs. We also summarize the challenges of NAbs therapeutics such as antibody-dependent enhancement and viral escape mutations. Such evidence is urgently needed to the development of antibody therapeutic interventions that are likely required to reduce the global burden of COVID-19.

Reliability of induced sputum test is greater than that of throat swab test for detecting SARS-CoV-2 in patients with COVID-19: A multi-center cross-sectional study.

We previously reported that sputum induction was more sensitive than throat swabs for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in two convalescent coronavirus disease 2019 (COVID-19) patients; however, the value and safety of induced sputum testing require further study. We conducted a prospective multi-center cross-sectional study to compare induced sputum to throat swabs for SARS-CoV-2 detection. Confirmed COVID-19 patients from six hospitals in six cities across China who received one or more negative RT-PCR result for SARS-CoV-2 were enrolled, and paired specimens (induced sputum and throat swabs; 56 cases) were assayed. In three paired samples, both the induced sputum and throat swabs were positive for SARS-CoV-2. The positive rate for induced sputum was significantly higher than for throat swabs both overall (28.6% vs 5.4%, respectively; p < 0.01). Patients were divided according to time span from onset of illness to sample collection into the more-than-30-day (n = 26) and less-than-30-day (n = 30) groups. The positive rate for induced sputum was also significantly higher than for throat swabs in the less-than-30-day group (53.3% vs 10.0%, respectively; p < 0.001). For the more-than-30-day group, all paired samples were negative for SARS-CoV-2. Blood oxygen saturation, respiratory rate, and heart rate remained stable during sputum induction and no staff were infected. Because induced sputum is more reliable and has a lower false-negative rate than throat swabs, we believe induced sputum is more useful for the confirmation of COVID-19 and is safer as a criterion for release from quarantine.