Tracking of Mutational Signature of SARS-CoV-2 Omicron on Distinct Continents and Little Difference was Found.

The Omicron variant is currently ravaging the world, raising serious concern globally. Monitoring genomic variations and determining their influence on biological features are critical for tracing its ongoing transmission and facilitating effective measures. Based on large-scale sequences from different continents, this study found that: (i) The genetic diversity of Omicron is much lower than that of the Delta variant. Still, eight deletions (Del 1-8) and 1 insertion, as well as 130 SNPs, were detected on the Omicron genomes, with two deletions (Del 3 and 4) and 38 SNPs commonly detected on all continents and exhibiting high-occurring frequencies. (ii) Four groups of tightly linked SNPs (linkage I-IV) were detected, among which linkage I, containing 38 SNPs, with 6 located in the RBD, increased its occurring frequency remarkably over time. (iii) The third codons of the Omicron shouldered the most mutation pressures, while the second codons presented the least flexibility. (iv) Four major mutants with amino acid substitutions in the RBD were detected, and further structural analysis suggested that the substitutions did not alter the viral receptor binding ability greatly. It was inferred that though the Omicron genome harbored great changes in antigenicity and remarkable ability to evade immunity, it was immune-pressure selected. This study tracked mutational signatures of Omicron variant and the potential biological significance of the SNPs, and the linkages await further functional verification.

Analysis of Continuous Mutation and Evolution on Circulating SARS-CoV-2

Monitoring the mutation and evolution of the virus is important for tracing its ongoing transmission and facilitating effective vaccine development. A total of 342 complete genomic sequences of SARS-CoV-2 were analyzed in this study. Compared to the reference genome reported in December 2019, 465 mutations were found, among which, 347 occurred in only 1 sequence, while 26 occurred in more than 5 sequences. For these 26 further identified as SNPs, 14 were closely linked and were grouped into 5 profiles. Phylogenetic analysis revealed the sequences formed 2 major groups. Most of the sequences in late period (March and April) constituted the Cluster II, while the sequences before March in this study and the reported S/L and A/B/C types in previous studies were all in Cluster I. The distributions of some mutations were specific geographically or temporally, the potential effect of which on the transmission and pathogenicity of SARS-CoV-2 deserves further evaluation and monitoring. Two mutations were found in the receptor-binding domain (RBD) but outside the receptor-binding motif (RBM), indicating that mutations may only have marginal biological effects but merit further attention. The observed novel sequence divergence is of great significance to the study of the transmission, pathogenicity, and development of an effective vaccine for SARS-CoV-2.

Persisting Chemosensory Impairments in 366 Healthcare Workers Following COVID-19: An 11-Month Follow-up. (preprint)

Background and Objectives: Olfactory and gustatory dysfunctions (OD, GD) are prevalent symptoms following COVID-19 and persist in 6%-44% of individuals in the first months after the infection. As only few reports have described their prognosis more than 6 months later, the main objective of this study was to assess the prevalence of OD and GD 11 months after COVID-19. We also aimed to determine test-retest reliability of subjective chemosensory ratings for the follow-up of chemosensory sensitivity, as this measure is often used for remote follow-up. Methods: Inclusion criteria included a PCR-confirmed SARS-CoV-2 infection; exclusion criteria were the presence of other respiratory infections and chronic sinusitis. To assess whether OD and GD had changed compared to pre-pandemic levels, we designed an observational study and distributed an online questionnaire assessing quantitative chemosensory function to healthcare workers 5 and 11 months after COVID-19. Specifically, we assessed olfaction, gustation, and trigeminal sensitivity (10-point visual analog scale) and function (4-point Likert scale) separately. We further assessed clinically relevant OD using the Chemosensory Perception Test, a psychophysical test designed to provide a reliable remote olfactory evaluation. Qualitative chemosensory dysfunction was also assessed. Results: We included a total of 366 participants (mean age of 44.8 years old (SD: 11.7)). They completed the last online questionnaire 10.6 months (SD: 0.7) after the onset of COVID-19 symptoms. Of all participants, 307 (83.9%) and 301 (82.2%) individuals retrospectively reported lower olfactory or gustatory sensitivity during the acute phase of COVID-19. Eleven months later, 184 (50.3%) and 163 (44.5%) indicated reduced chemosensory sensitivity, 32.2% reported impairment of olfactory function while 24.9% exhibited clinically relevant OD. Three variables predicted OD at follow-up, namely chest pain and GD during COVID-19 and presence of phantosmia at 5 months. Olfactory sensitivity ratings had a high test-retest reliability (intraclass correlation coefficient: 0.818 (95% CI: 0.760 - 0.860)) Discussion: This study suggests that chemosensory dysfunctions persist in a third of COVID-19 patients 11 months after COVID-19. Subjective measures have a high test-retest reliability and thus can be used to monitor post-COVID-19 OD. OD appears to be a common long-term symptom of COVID-19 important to consider when treating patients.

A Study of Work Insecurity, Work Stress, and Organizational Commitment of University Staffs under the COVID-19 Pandemic

The COVID-19 outbreak has an impact on the world. Activities in all walks of life have been suspended to avoid risks to the masses. School organizations are also facing a lot of changes and challenges. Previous studies have not yet discussed the work stress and insecurity of school staffs in response to the increased workload of the COVID-19 pandemic. The purposes of this study are to examine the relationships between work insecurity, work stress, and organizational commitment during the COVID-19 pandemic. This study employed online survey method to collect data from staffs of universities in Kaohsiung and Pingtung and used structural equation modelling to analyse data. The results indicated that male has more work stress than female;the older and the longer the staff have higher organizational commitments;married staffs have higher organizational commitments than unmarried staffs. Work insecurity has significantly positive influences on work stress. Work insecurity and work stress have significantly negative influences on organizational commitment. This study provides suggestions for educational organizations and future research.

Biological Significance of the Genomic Variation and Structural Dynamics of SARS-CoV-2 B.1.617.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been emerging and circulating globally since the start of the COVID-19 pandemic, of which B.1.617 lineage that was first reported in India at the end of 2020, soon became predominant. Tracing genomic variations and understanding their impact on the viral properties are the foundations for the vaccine and drug development and for the mitigation measures to be taken or lifted. In this study, 1,051 near-complete genomes and 1,559 spike (S) sequences belonging to the B.1.617 were analyzed. A genome-wide spread of single nucleotide polymorphisms (SNPs) was identified. Of the high frequency mutations identified, 61% (11/18) involved structural proteins, despite two third of the viral genome encoding nonstructural proteins. There were 22 positive selection sites, mostly distributed across the S protein, of which 16 were led by non-C to U transition and should be of a special attention. Haplotype network revealed that a large number of daughter haplotypes were continually derived throughout the pandemic, of which H177, H181 H219 and H286 from the ancestor haplotype H176 of B.1.617.2 were widely prevalent. Besides the well known substitutions of L452R, P681R and deletions of E156 and F157, as well as the potential biological significance, structural analysis in this study still indicated that new amino acid changes in B.1.617, such as E484Q and N501Y, had reshaped the viral bonding network, and increasingly sequenced N501Y mutant with a potential enhanced binding ability was detected in many other countries in the follow-up monitoring. Although we can't conclude the properties of all the mutants including N501Y thoroughly, it merits focusing on their spread epidemically and biologically.

Clinical characteristics of pregnant women infected with Coronavirus Disease 2019 in China: a nationwide case-control study (preprint)

OBJECTIVETo formally compare the clinical course of Coronavirus disease 2019 (COVID-19) in pregnant women with their nonpregnant counterparts. METHODSClinical data of pregnant women with confirmed COVID-19 in the designated hospitals of mainland China were retrieved up to April 12, 2020 through an epidemic reporting system maintained at the National Health Commission of the Peoples Republic China. Each pregnant patient was randomly matched to a nonpregnant woman with confirmed COVID-19 in the same hospital as control, then their clinical courses were formally compared. RESULTS138 pregnant women had been identified as confirmed COVID-19 cases. Among them, 17 severe cases and 1 maternal death were recorded, which was less than their nonpregnant peers (23 severe cases and 3 death). 57.2% had been infected with SARS-CoV-2 during the third trimester, including 13 severe cases and 1 maternal death. 7.3% of pregnant patients had diarrhea and 3.6% had nausea or vomiting, compared with related proportion as 15.2% (OR: 0.38, 95%CI: 0.15, 0.96) and 10.1% (OR: 0.25, 95%CI: 0.07, 0.89) in nonpregnant patients. Pregnant patients infected with SARS-CoV-2 in early pregnancy presented similar laboratory tests with their nonpregnant peers, however, with pregnancy progresses, increased inflammation, coagulation and hepatic injury markers happened more and more frequently (p<0.001) in pregnant patients. CONCLUSIONSBeing pregnant did not represent a risk for severe condition when compared with their nonpregnant peers. Patients infected with SARS-CoV-2 in early pregnancy were even at lower risk of severe illness than those infected in late pregnancy. What are the novel findings of this work?Compared with non-pregnant COVID-19 patients, pregnant patients tend to present less symptom, had unique laboratory findings, and tend to at lower risk of COVID-19-related death. Patients infected with SARS-CoV-2 in the early pregnancy tend to be in the less severe condition of illness than those infected in late pregnancy. What are the clinical implications of this work?Vital comparisons of the clinical course upon COVID-19 between pregnant and nonpregnant women in childbearing age are, unfortunately, lacking. Through formally comparisons between the two groups, the present study provides more reliable evidence towards the management of pregnant women with COVID-19.

Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine (preprint)

SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccine and the potential need for a third booster dose for the HCWs. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 31.2 AU/ml to 9.2 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 66.8 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly "no responders" but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which has implications for future booster strategies that the frontline HCWs, individuals with low serological response to 2 dose of vaccine and immune compromised patients could benefit from a third dose of inactivated vaccine.

COVID-19 Has Long Term Effects on Chemosensory Functions (preprint)

Importance: A number of studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Objective: To describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution at 3 to 7 months after infection. Design, Setting, and Participants: A follow-up study of 704 health care workers with a RT-PCR confirmed SARS-CoV-2 infection between 28/2/2020 and 14/6/2020 was conducted 3 to 7 months after onset of symptoms. Data were collected with an online questionnaire. Participant had to be [≥]18 years old without respiratory illness in the 2 weeks prior to questionnaire completion. Main outcomes and measures: Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Results: Among the 704 health care worker participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities were reported by 81.3%, 81.5% and 48.0% respectively. Three to seven months later, reduced sensitivity was still reported by 52.0%, 41.9% and 23.3% respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. Conclusions and relevance: A significant proportion of COVID-19 cases have persistent chemosensory impairments at 3 to 7 months after their infection but the majority of those who had completely lost their olfactory, gustatory and trigeminal sensitivity have improved. Given the possible neurological underpinnings of this observation and the important number of individuals infected with SARS-CoV-2, further longitudinal studies are needed to better characterize this phenotype and to report eventual post-COVID-19 neurological sequelae.

Analysis of Continuous Mutation and Evolution on Circulating SARS-CoV-2.

Monitoring the mutation and evolution of the virus is important for tracing its ongoing transmission and facilitating effective vaccine development. A total of 342 complete genomic sequences of SARS-CoV-2 were analyzed in this study. Compared to the reference genome reported in December 2019, 465 mutations were found, among which, 347 occurred in only 1 sequence, while 26 occurred in more than 5 sequences. For these 26 further identified as SNPs, 14 were closely linked and were grouped into 5 profiles. Phylogenetic analysis revealed the sequences formed 2 major groups. Most of the sequences in late period (March and April) constituted the Cluster II, while the sequences before March in this study and the reported S/L and A/B/C types in previous studies were all in Cluster I. The distributions of some mutations were specific geographically or temporally, the potential effect of which on the transmission and pathogenicity of SARS-CoV-2 deserves further evaluation and monitoring. Two mutations were found in the receptor-binding domain (RBD) but outside the receptor-binding motif (RBM), indicating that mutations may only have marginal biological effects but merit further attention. The observed novel sequence divergence is of great significance to the study of the transmission, pathogenicity, and development of an effective vaccine for SARS-CoV-2.

JCS: An Explainable COVID-19 Diagnosis System by Joint Classification and Segmentation (preprint)

Recently, the coronavirus disease 2019 (COVID-19) has caused a pandemic disease in over 200 countries, influencing billions of humans. To control the infection, identifying and separating the infected people is the most crucial step. The main diagnostic tool is the Reverse Transcription Polymerase Chain Reaction (RT-PCR) test. Still, the sensitivity of the RT-PCR test is not high enough to effectively prevent the pandemic. The chest CT scan test provides a valuable complementary tool to the RT-PCR test, and it can identify the patients in the early-stage with high sensitivity. However, the chest CT scan test is usually time-consuming, requiring about 21.5 minutes per case. This paper develops a novel Joint Classification and Segmentation (JCS) system to perform real-time and explainable COVID-19 chest CT diagnosis. To train our JCS system, we construct a large scale COVID-19 Classification and Segmentation (COVID-CS) dataset, with 144,167 chest CT images of 400 COVID-19 patients and 350 uninfected cases. 3,855 chest CT images of 200 patients are annotated with fine-grained pixel-level labels of opacifications, which are increased attenuation of the lung parenchyma. We also have annotated lesion counts, opacification areas, and locations and thus benefit various diagnosis aspects. Extensive experiments demonstrate that the proposed JCS diagnosis system is very efficient for COVID-19 classification and segmentation. It obtains an average sensitivity of 95.0% and a specificity of 93.0% on the classification test set, and 78.5% Dice score on the segmentation test set of our COVID-CS dataset. The COVID-CS dataset and code are available at https://github.com/yuhuan-wu/JCS.