Viral Pneumonia during the COVID-19 Pandemic, 2019-2021 Evoking Needs for SARS-CoV-2 and Additional Vaccinations.

Coronaviruses can cause pneumonia, with clinical symptoms that may be similar to the symptoms of other viral pneumonias. To our knowledge, there have been no reports regarding cases of pneumonia caused by coronaviruses and other viruses among hospitalized patients in the past 3 years before and during coronavirus disease 2019 (COVID-19). Here, we analysed the causes of viral pneumonia among hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic (2019-2021). Between September 2019 and April 2021, patients hospitalized at Shuang Ho Hospital in north Taiwan with a diagnosis of pneumonia were enrolled in this study. Age, sex, onset date, and season of occurrence were recorded. Respiratory tract pathogens were identified with molecular detection using the FilmArray® platform from nasopharyngeal swabs. In total, 1147 patients (128 patients aged <18 years and 1019 patients aged ≥18 years) with pneumonia and identified respiratory tract pathogens were assessed. Among the 128 children with pneumonia, the dominant viral respiratory pathogen was rhinovirus (24.2%), followed by respiratory syncytial virus (RSV; 22.7%), parainfluenza virus (1 + 2 + 3 + 4) (17.2%), adenovirus (12.5%), metapneumovirus (9.4%), coronavirus (1.6%), and influenza virus (A + B) (1.6%). Among the 1019 adults with pneumonia, the dominant viral respiratory pathogen was rhinovirus (5.0%), followed by RSV (2.0%), coronavirus (2.0%), metapneumovirus (1.5%), parainfluenza virus (1 + 2 + 3 + 4) (1.1%), adenovirus (0.7%), and influenza virus (A + B) (0%). From 2019-2021, older patients (aged >65 years) with pneumonia tested positive for coronavirus most commonly in autumn. Coronavirus was not detected during summer in children or adults. Among children aged 0-6 years, RSV was the most common viral pathogen, and RSV infection occurred most often in autumn. Metapneumovirus infection occurred most often in spring in both children and adults. In contrast, influenza virus was not detected in patients with pneumonia in any season among children or adults from January 2020 to April 2021. Among all patients with pneumonia, the most common viral pathogens were rhinovirus in spring, adenovirus and rhinovirus in summer, RSV and rhinovirus in autumn, and parainfluenza virus in winter. Among children aged 0-6 years, RSV, rhinovirus, and adenovirus were detected in all seasons during the study period. In conclusion, the proportion of pneumonia cases caused by a viral pathogen was higher in children than the proportion in adults. The COVID-19 pandemic period evoked a need for SARS-CoV-2 (severe acute respiratory disease coronavirus 2) vaccination to prevent the severe complications of COVID-19. However, other viruses were also found. Vaccines for influenza were clinically applied. Active vaccines for other viral pathogens such as RSV, rhinovirus, metapneuomoccus, parainfluenza, and adenovirus may need to be developed for special groups in the future.

Using a BBWM-PROMETHEE model for evaluating mobile commerce service quality: A case study of food delivery platform

In the age of COVID-19, many governments imposed social distancing, work-from-home, and crowd control measures, which continue to affect economic development and forces service providers to be increasingly reliant on e-commerce and m-commerce platform technology. Moreover, due to the availability of 5G network speeds, cell phone applications and the Internet services have become indispensable for future smart lifestyles, prompting brick-and-mortar businesses to shift their sales models to mobile network operators (MNOs). To popularize the use of m-commerce, it is critical to ensure that service platforms operate well and give the customer what they want. It is thus essential to create a comprehensive and complete performance framework for the evaluation of m-commerce services. In this paper, a hybrid model is developed to explore this issue and the effectiveness and robustness of the model is illustrated by an application to two major food delivery platforms in Taiwan. The Bayesian Best Worst Method (BBWM) is applied to identify the criteria weights and ranks. The judgments of 14 experts are integrated to obtain the optimal group criteria weights. The performance data were obtained from a survey of 210 experienced users of these delivery platforms. The difference between the actual performance of each delivery platform and the aspiration level (AL) was calculated using the modified Preference Ranking Organization Method for Enrichment Evaluations (modified PROMETHEE) to determine an overall score for each delivery platform. A sensitivity analysis was also conducted and comparison made with other Multiple Criteria Decision-Making (MCDM) methods. The results show that information security and privacy, integrity, and mobile transaction service are the most important criteria, with Food Panda performing better than the other mobile food delivery service provider. The proposed evaluation framework is useful for performance evaluation of mobile commerce service quality, and providing effective suggestions to assist decision-makers in creating development strategies.

Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused devastating impacts on the public health and the global economy. Rapid viral antigenic evolution has led to the continual generation of new variants. Of special note is the recently expanding Omicron subvariants that are capable of immune evasion from most of the existing neutralizing antibodies (nAbs). This has posed new challenges for the prevention and treatment of COVID-19. Therefore, exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In sharp contrast to the massive accumulation of mutations within the SARS-CoV-2 receptor-binding domain (RBD), the S2 fusion subunit has remained highly conserved among variants. Hence, S2-based therapeutics may provide effective cross-protection against new SARS-CoV-2 variants. Here, we summarize the most recently developed broad-spectrum fusion inhibitors (e.g., nAbs, peptides, proteins, and small-molecule compounds) and candidate vaccines targeting the conserved elements in SARS-CoV-2 S2 subunit. The main focus includes all the targetable S2 elements, namely, the fusion peptide, stem helix, and heptad repeats 1 and 2 (HR1-HR2) bundle. Moreover, we provide a detailed summary of the characteristics and action-mechanisms for each class of cross-reactive fusion inhibitors, which should guide and promote future design of S2-based inhibitors and vaccines against new coronaviruses.

A new and specific automated blood pressure device for exercise stress testing.

Blood pressure (BP) measurement plays a critical role in cardiac stress testing and is most commonly assessed manually. The emphasis of social distancing during the COVID-19 pandemic has renewed the interest in and the need for an automated BP device for incremental exercise stress testing. We assessed the accuracy of a new automated blood pressure device specifically manufactured for cardiac stress testing. Thirty-five adults aged 35 ± 16 years were studied during an incremental stress test on the cycle ergometer. Three observers measured BP simultaneously, two listening to Korotkoff sounds using a dual-headed stethoscope and one using headphones to listen to sounds generated by an automated BP device. With increasing workload, systolic BP increased progressively without significant differences in BP readings between any observer compared with the automated monitor at any stage during exercise. Systolic BP obtained with the BP machine was strongly correlated with those obtained by the stethoscope observers (r = 0.96) and the observer with headphones (r = 0.95). Diastolic BP obtained with the BP machine was moderately and significantly associated with those obtained by the stethoscope observers (r = 0.75) and the observer with headphones (r = 0.75). The automated BP monitor specifically made for cardiac stress testing accurately measured both systolic and diastolic blood pressure during exercise.

Search of Novel Small Molecule Inhibitors for the Main Protease of SARS-CoV-2.

The current outbreak of coronavirus disease 2019 (COVID-19) has prompted the necessity of efficient treatment strategies. The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Main protease (Mpro), also called 3-chymotrypsin-like protease (3CL protease), plays an essential role in cleaving virus polyproteins for the functional replication complex. Therefore, Mpro is a promising drug target for COVID-19 therapy. Through molecular modelling, docking and a protease activity assay, we found four novel inhibitors targeting Mpro with the half maximal inhibitory concentration (IC50) and their binding affinities shown by the dissociation constants (KDs). Our new inhibitors CB-21, CB-25, CP-1 and LC24-20 have IC50s at 14.88 µM (95% Confidence Interval (95% CI): 10.35 µM to 20.48 µM), 22.74 µM (95% CI: 13.01 µM to 38.16 µM), 18.54µM (95% CI: 6.54 µM to 36.30 µM) and 32.87µM (95% CI: 18.37 µM to 54.80 µM)), respectively. The evaluation of interactions suggested that each inhibitor has a hydrogen bond or hydrophobic interactions with important residues, including the most essential catalytic residues: His41 and Cys145. All the four inhibitors have a much higher 50% lethal dose (LD50) compared with the well-known Mpro inhibitor GC376, demonstrating its low toxicity. These four inhibitors can be potential drug candidates for further in vitro and in vivo studies against COVID-19.

The Clinical Observation of Inflammation Theory for Depression: The Initiative of the Formosa Long COVID Multicenter Study (FOCuS).

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

Internet searches for "insomnia" and "suicide" mediated by stay-at-home behaviors in 45 countries during the first 12 months of the COVID-19 pandemic.

BACKGROUND: This study aimed to investigate (1) the mental health impacts (i.e., insomnia and suicide ideas) of the COVID-19 pandemic and (2) the mediation effects of stay-at-home levels on those impacts. METHODS: This study investigated monthly national COVID-19 deaths, stay-at-home levels, and internet searches for words for "insomnia" and "suicide" across 45 countries during the first year of the COVID-19 pandemic (March 1, 2020, to February 28, 2021). We used the changes of internet search volumes for "insomnia" and "suicide" (from the Google Trends database) to represent the mental health impacts, and the time of cell phone activity at the residence (from Google Location History) to estimate the stay-at-home effects. We computed the proportion mediated (PM) caused by stay-at-home levels in the COVID-19 impacts on insomnia and suicide ideas, respectively. RESULTS: Throughout the first year of the COVID-19 pandemic, national COVID-19 deaths significantly correlated to increased internet searches for "insomnia" but decreased searches for "suicide". In addition, the mediation effect was significant in the first six-month of COVID-19-related increases in insomnia (PM = 42.6 %, p = 0.016), but this effect was not significant (PM = 13.1 %, p = 0.270) in the second six-month. By contrast, the mediation effect was not significant in the first six-month of COVID-19-related decrease in suicide ideation (PM = 8.1 %, p = 0.180), but this effect was significant (PM = 39.6 %, p = 0.014) in the second six-month. CONCLUSIONS: Stay-at-home levels significantly mediated both increased insomnia and decreased suicide ideas, but within different time frames.

Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge.

Objective: To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. Methods: A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. Results: The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28 (3.31, 8.13) vs. 9.10 (4.37, 15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13 (0.00, 0.09) vs. 0.12 (0.03, 0.41), p<0.05; 0.02 (0.00, 0.14) vs. 1.94 (0.54, 6.40), p<0.05; 5.46 (2.41, 9.26) vs. 73.63 (54.63, 86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13). Conclusion: Unvaccinated children may be an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2), which indicated an urgent need of vaccination for this particular population.

AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity.

Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at S511, which triggers IRF3 recruitment and the assembly of MAVS or STING signalosomes. Consistently, ablation or inhibition of AMPK, knockin of TBK1-S511A, or increased glucose levels compromised nucleic acid sensing, while boosting AMPK-TBK1 cascade by AICAR or TBK1-S511E knockin improves antiviral immunity substantially in various animal models. Thus, we identify TBK1 as an AMPK substrate, reveal the molecular mechanism coupling a dual sensing of glucose and nuclei acids, and report its physiological necessity in antiviral defense.

Why teaching innovation matters: Evidence from a pre- versus peri-COVID-19 pandemic comparison of student evaluation data.

The COVID-19 pandemic has robustly affected global education environments, so higher education institutions need to emphasize innovation and creativity in educational methods for teachers to improve their teaching performance as well as enhance the engagement and motivation of students in this changing environment. Accordingly, it is essential to discuss the role of teaching innovation in the setting of the COVID-19 pandemic compared to the pre-COVID-19 period. The aim of this study is to empirically validate the importance of teaching innovation in student evaluation of teaching before and during the COVID-19 pandemic. Data were collected from the medical college of a comprehensive university in Taiwan and were subjected to t-tests and multiple linear regression analysis. Findings from a quantitative study with 44 teachers revealed that teaching innovation was positively correlated to student evaluation of teaching. We also found that teachers who implemented teaching innovation strategies performed better than those teachers who used conventional teaching strategies on student evaluation of teaching. In particular, teaching innovative teachers had improvement in student evaluation of teaching during the time of the COVID-19 pandemic, but not non-teaching innovative teachers. The evidence from this study suggests that teaching innovation can not only enhance teachers' teaching development and performance but also boost students' motivation for learning, especially in the time of the COVID-19 pandemic. Our findings have important implications for future research on teaching innovation and for higher education institutions and faculty wishing to provide high-quality learning environments to their students.

Multi-label classification for biomedical literature: an overview of the BioCreative VII LitCovid Track for COVID-19 literature topic annotations.

The coronavirus disease 2019 (COVID-19) pandemic has been severely impacting global society since December 2019. The related findings such as vaccine and drug development have been reported in biomedical literature-at a rate of about 10 000 articles on COVID-19 per month. Such rapid growth significantly challenges manual curation and interpretation. For instance, LitCovid is a literature database of COVID-19-related articles in PubMed, which has accumulated more than 200 000 articles with millions of accesses each month by users worldwide. One primary curation task is to assign up to eight topics (e.g. Diagnosis and Treatment) to the articles in LitCovid. The annotated topics have been widely used for navigating the COVID literature, rapidly locating articles of interest and other downstream studies. However, annotating the topics has been the bottleneck of manual curation. Despite the continuing advances in biomedical text-mining methods, few have been dedicated to topic annotations in COVID-19 literature. To close the gap, we organized the BioCreative LitCovid track to call for a community effort to tackle automated topic annotation for COVID-19 literature. The BioCreative LitCovid dataset-consisting of over 30 000 articles with manually reviewed topics-was created for training and testing. It is one of the largest multi-label classification datasets in biomedical scientific literature. Nineteen teams worldwide participated and made 80 submissions in total. Most teams used hybrid systems based on transformers. The highest performing submissions achieved 0.8875, 0.9181 and 0.9394 for macro-F1-score, micro-F1-score and instance-based F1-score, respectively. Notably, these scores are substantially higher (e.g. 12%, higher for macro F1-score) than the corresponding scores of the state-of-art multi-label classification method. The level of participation and results demonstrate a successful track and help close the gap between dataset curation and method development. The dataset is publicly available via https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/ for benchmarking and further development. Database URL https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/.

A BERT-based ensemble learning approach for the BioCreative VII challenges: full-text chemical identification and multi-label classification in PubMed articles.

In this research, we explored various state-of-the-art biomedical-specific pre-trained Bidirectional Encoder Representations from Transformers (BERT) models for the National Library of Medicine - Chemistry (NLM CHEM) and LitCovid tracks in the BioCreative VII Challenge, and propose a BERT-based ensemble learning approach to integrate the advantages of various models to improve the system's performance. The experimental results of the NLM-CHEM track demonstrate that our method can achieve remarkable performance, with F1-scores of 85% and 91.8% in strict and approximate evaluations, respectively. Moreover, the proposed Medical Subject Headings identifier (MeSH ID) normalization algorithm is effective in entity normalization, which achieved a F1-score of about 80% in both strict and approximate evaluations. For the LitCovid track, the proposed method is also effective in detecting topics in the Coronavirus disease 2019 (COVID-19) literature, which outperformed the compared methods and achieve state-of-the-art performance in the LitCovid corpus. Database URL: https://www.ncbi.nlm.nih.gov/research/coronavirus/.

A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding.

The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our in-vitro biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases.

An engineered 5-helix bundle derived from SARS-CoV-2 S2 pre-binds sarbecoviral spike at both serological- and endosomal-pH to inhibit virus entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related sarbecoviruses enter host cells by receptor-recognition and membrane-fusion. An indispensable step in fusion is the formation of 6-helix bundle by viral spike heptad repeats 1 and 2 (HR1 and HR2). Here, we report the construction of 5-helix bundle (5HB) proteins for virus infection inhibition. The optimal construct inhibits SARS-CoV-2 pseudovirus entry with sub-micromolar IC50. Unlike HR2-based peptides that cannot bind spike in the pre-fusion conformation, 5HB features with the capability of binding to pre-fusion spike. Furthermore, 5HB binds viral HR2 at both serological- and endosomal-pH, highlighting its entry-inhibition capacity when SARS-CoV-2 enters via either cell membrane fusion or endosomal route. Finally, we show that 5HB could neutralize S-mediated entry of the predominant SARS-CoV-2 variants and a wide spectrum of sarbecoviruses. These data provide proof-of-concept evidence that 5HB might be developed for the prevention and treatment of SARS-CoV-2 and other emerging sarbecovirus infections.

Identification of serum metabolites enhancing inflammatory responses in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.

Epidemiology, Clinical Features, and Unusual Complications of Norovirus Infection in Taiwan: What We Know after Rotavirus Vaccines.

Noroviruses (NoVs) are one of the emerging and rapidly spreading groups of pathogens threatening human health. A reduction in sporadic NoV infections was noted following the start of the COVID-19 pandemic, but the return of NoV gastroenteritis during the COVID-19 pandemic has been noted recently. Research in recent years has shown that different virus strains are associated with different clinical characteristics; moreover, there is a paucity of research into extraintestinal or unusual complications that may be associated with NoV. The genomic diversity of circulating NoVs is also complex and may vary significantly. Therefore, this short narrative review focuses on sharing the Taiwan experience of NoV infection including epidemiology, clinical features, and complications following suboptimal rotavirus immunization in Taiwan (after October 2006). We also highlight the unusual complications associated with NoV infections and the impacts of NoV infection during the COVID-19 pandemic in the literature for possible future research directions. To conclude, further research is needed to quantify the burden of NoV across the spectrum of disease severity in Taiwan. The evidence of the connection between NoV and the unusual complications is still lacking.

Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge

Objective To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. Methods A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2;confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared;The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. Results The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue;they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10

Broad Impacts of Coronavirus Disease 2019 (COVID-19) Pandemic on Acute Respiratory Infections in China: An Observational Study.

BACKGROUND: To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. RESULTS: Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

Fever, Tachypnea, and Monocyte Distribution Width Predicts Length of Stay for Patients with COVID-19: A Pioneer Study.

(1) Background: Our study investigated whether monocyte distribution width (MDW) could be used in emergency department (ED) settings as a predictor of prolonged length of stay (LOS) for patients with COVID-19. (2) Methods: A retrospective cohort study was conducted; patients presenting to the ED of an academic hospital with confirmed COVID-19 were enrolled. Multivariable logistic regression models were used to obtain the odds ratios (ORs) for predictors of an LOS of >14 days. A validation study for the association between MDW and cycle of threshold (Ct) value was performed. (3) Results: Fever > 38 °C (OR: 2.82, 95% CI, 1.13-7.02, p = 0.0259), tachypnea (OR: 4.76, 95% CI, 1.67-13.55, p = 0.0034), and MDW ≥ 21 (OR: 5.67, 95% CI, 1.19-27.10, p = 0.0269) were robust significant predictors of an LOS of >14 days. We developed a new scoring system in which patients were assigned 1 point for fever > 38 °C, 2 points for tachypnea > 20 breath/min, and 3 points for MDW ≥ 21. The optimal cutoff was a score of ≥2. MDW was negatively associated with Ct value (ß: -0.32 per day, standard error = 0.12, p = 0.0099). (4) Conclusions: Elevated MDW was associated with a prolonged LOS.

Long-term immune responses in patients with confirmed novel coronavirus disease-2019: a 9-month prospective cohort study in Shanghai, China.

BACKGROUND: The duration of antibodies against SARS-CoV-2 in Covid-19 patients remains uncertain. Longitudinal serological studies are needed to prevent disease and transmission of the virus. METHODS: In 2020, 414 blood samples were tested, obtained from 157 confirmed Covid-19 patients, in a prospective cohort study in Shanghai. RESULTS: The seropositive rate of IgM peaked at 40.5% (17/42) within 1 month after illness onset and then declined. The seropositive rate of IgG was 90.6% (58/64) after 2 months, remained above 85% from 2 to 9 months and was 90.9% (40/44) after 9 months. Generalized estimating equations models suggested that IgM (P < 0.001) but not IgG significantly decreased over time. Age ≥ 40 years (adjusted odds ratio [aOR] 4.531; 95% confidence interval [CI] 1.879-10.932), and cigarette smoking (aOR 0.344; 95% CI 0.124-0.951) were associated with IgG, and age ≥ 40 years (aOR 2.820; 95% CI 1.579-5.036) was associated with IgM. After seroconversion, over 90% and 75.1% of subjects were estimated to remain IgG-positive 220 and 254 days, respectively. Of 1420 self-reported symptoms questionnaires, only 5% reported symptoms 9 months after onset. CONCLUSIONS: In patients with a history of natural infection, anti-SARS-CoV-2 IgG is long-lived, being present for at least 9 months after illness onset. The long duration of natural immunity can mitigate and eliminate Covid-19 and the ongoing pandemic.