Evolution of viral pneumonia before and after COVID-19 pandemic---A retrospective study based on respiratory viral nucleic acid results from 5,928 patients (preprint)

Background: There are limited data on etiology of viral pneumonia under the impact of COVID-19 pandemic. We aimed to investigate the changes of viral pneumonia before and after COVID-19 pandemic among patients diagnosed with pneumonia. Methods: This is a single-center retrospective study. Patients hospitalized with pneumonia during January 1,2016 and Dec 31,2021 in West China Hospital were included and divided into pre- and post-COVID-19 groups according to the point of COVID-19 outbreak in China which was December 8,2019. Results of the 13 viral nucleic acid tests were compared between the two groups. Results: 5,928 patients were analyzed,3,945 in the pre-COVID-19 group while 1,983 in the post-COVID-19. Respiratory viral nucleic acid screening proportion was riseing after COVID-19 (14.8％ VS 22.8％).But the positive rate of post-COVID-19 total virus and Influenza virus had decreased 23.3% and 18.3%, respectively,p＜0.05. The top three viral pneumonia were InfAH1N1(2009),Human Rhinovirus,Human Adenovirus before COVID-19, while HRV, Human Parainfluenza virus, Human Respiratory Syncytial virus after COVID-19 pandemic. Notebly,InfAH1N1(2009) pneumonia decreased to 0％ after the pandemic. Conclusions: Proportion of viral pneumonia has significantly decreased under the impact of COVID-19 pneumonia and the incidence of InfAH1N1(2009) pneumonia is almost 0.

Estimates of Power Shortages and Affected Populations during the Initial Period of the Ukrainian-Russian Conflict

Since the outbreak of the Ukrainian-Russian conflict on 24 February 2022, Ukraine’s economy, society, and cities have been devastated and struck on multiple fronts, with large numbers of refugees fleeing to neighboring countries. The lighting systems in Ukrainian cities have been severely restricted due to Russian missile bombing and curfew policies. The power shortages adversely affected the livelihoods of the Ukrainian residents dramatically. For a timely assessment of the power shortages’ extent and the affected population in Ukraine, this study tracked the dynamics of nighttime light emissions in Ukraine based on the newly developed daily Black Marble product (VNP46A2) from NASA. The results show that the average light radiance in Ukrainian urban areas has decreased by about 37% since the eruption of the war, with Kiev city being the most dramatic region, having a post-conflict decrease of about 51%. In addition, by introducing near-real-time population data, we have implemented a survey of the affected population in Ukraine suffering from war-induced power shortages. Estimates show that about 17.3 million Ukrainian residents were affected by power shortages. In more detail, the number of children under 10 years old was about 2.35 million (about 5.24% of the total population), while the number of elderly people over 60 years old was about 3.53 million (about 7.86% of the total population). Generally, the results of this study could contribute positively to the timely assessment of the impact of the conflict and the implementation of humanitarian relief.

Molecular basis of broad neutralization against SARS-CoV-2 variants including Omicron by a human antibody (preprint)

Omicron, a newly emerging SARS-CoV-2 variant, carried a large number of mutations in the spike protein leading to an unprecedented evasion from many neutralizing antibodies (nAbs). Here, we performed a head-to-head comparison of Omicron with other existing highly evasive variants in terms of their reduced sensitivities to antibodies, and found that Omicron variant is significantly more evasive than Beta and Mu variants. Of note, some key mutations occur in the conserved epitopes identified previously, especially in the binding sites of Class 4 nAbs, contributing to the increased Ab evasion. We also reported a broadly nAb (bnAb), VacW-209, which effectively neutralized all tested SARS-CoV-2 variants and even SARS-CoV. Finally, we determined six cryo-electron microscopy structures of VacW-209 complexed with the spike ectodomains of wild-type, Delta, Mu, C.1.2, Omicron, and SARS-CoV, and revealed the molecular basis of the broadly neutralizing activities of VacW-209 against SARS-CoV-2 variants. Overall, Omicron has once again raised the alarm over virus variation with significantly compromised neutralization. BnAbs targeting more conserved epitopes among variants will continue to play a key role in pandemic control and prevention. One sentence summaryStructural and functional analyses reveal that a human antibody named VacW-209 confers broad neutralization against SARS-CoV-2 variants including Omicron by recognizing a highly conserved epitope.

Etiology and Chinese Medicine Screening of Severe COVID-19 Based on Multiomics and Serum Pharmacology (preprint)

Background: At present, scholars believe that severe COVID-19 is related to a variety of basic diseases, and we also observe this point using multi-omics method. The latest sequencing data of severe COVID-19 patients were combined to analyze the pathological mechanism, and pharmacological experimental research on local drugs was conducted, and a compound ingredient was found to have potential medicinal value. Results Here, we observed, for patients with severe COVID-19 disease, the differential miRNA expression is mainly low but having higher expression of mRNA. These differential mRNA expressions are associated with the activation of inflammatory pathways and ultimately with hypoxia and coagulation. Using database analysis, we found that Yi Xin Tong Mai Granule(YXTMG) might regulate COVID-19 through Toll-like receptor signaling pathway by acting on different immune targets. We found a new molecular mechanism for COVID-19 to turn the crisis around, the down-regulated miR-181a-5p mediates the up-regulation of PLAU and SERPINE1 molecules to cause cardiovascular adverse events, and YXTMG may prevent it. At the same time, molecular docking indicated that the its various components have anti-inflammatory activity. In vitro studies, we confirmed that YXTMG had antioxidant and anti-inflammatory activities. Conclusions The study has supplemented the potential mechanism for the conversion of mild to critical COVID-19 disease and screened the Chinese medicines for improving these factors, providing methodological reference for disease pathology and drug development.

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist to circulating variants (preprint)

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 still ravaging 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. Significantly, both antibodies confer good mutation resistance to 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, and can also inform the design of pan-sarbecovirus vaccines.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 variants (preprint)

SARS-CoV-2 and its variants are raging worldwide. Unfortunately, the global vaccination is not efficient enough to attain a vaccine-based herd-immunity and yet no special and effective drug is developed to contain the spread of the disease. Previously we have identified CD147 as a novel receptor for SARS-CoV-2 infection. Here, we demonstrated that CD147 antibody effectively inhibits infection and cytokine storm caused by SARS-CoV-2 variants. In CD147KO VeroE6 cells, infections of SARS-CoV-2, its variants (B.1.1.7, B.1.351) and pseudovirus mutants (B.1.1.7, B.1.351, B.1.525, B.1.526 (S477N), B.1.526 (E484K), P.1, P.2, B.1.617.1, B.1.617.2) were decreased. Meanwhile, CD147 antibody effectively blocked the entry of variants and pseudomutants in VeroE6 cells, and inhibited the expression of cytokines. A model of SARS-CoV-2-infected hCD147 transgenic mice was constructed, which recapitulated the features of exudative diffuse alveolar damage and dynamic immune responses of COVID-19. CD147 antibody could effectively clear the virus and alveolar exudation, resolving the pneumonia. We found the elevated level of cyclophilin A (CyPA) in plasma of severe/critical cases, and identified CyPA as the most important proinflammatory intermediate causing cytokine storm. Mechanistically, spike protein of SARS-CoV-2 bound to CD147 and initiated the JAK-STAT pathway, which induced expression of CyPA. CyPA reciprocally bound to CD147, triggered MAPK pathway and consequently mediated the expression of cytokine and chemokine. In conclusion, CD147 is a critical target for SARS-CoV-2 variants and CD147 antibody is a promising drug to control the new wave of COVID-19 epidemic.

Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

Spike mutations in SARS-CoV-2 variants confer resistance to antibody neutralization (preprint)

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS CoV 2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS CoV 2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N E484K N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

Single-dose immunization with a chimpanzee adenovirus-based vaccine induces sustained and protective immunity against SARS-CoV-2 infection (preprint)

The development of an effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we present three chimpanzee adenovirus vaccines that express either the full-length spike (ChAdTS-S), or receptor-binding domain (RBD) with two different signal sequences (ChAdTS-RBD and ChAdTS-RBDs). Single-dose intranasal or intramuscular immunization induced robust and sustained neutralizing antibody responses in BALB/c mice, with ChAdTS-S being superior to ChAdTS-RBD and ChAdTS-RBDs. Intranasal immunization appeared to induce a predominately Th2-based response whereas intramuscular administration resulted in a predominately Th1 response. The neutralizing activity against several circulating SARS-CoV-2 variants remained unaffected for mice serum but reduced for rhesus macaque serum. Importantly, immunization with ChAdTS-S via either route induced protective immunity against high-dose challenge with live SARS-CoV-2 in rhesus macaques. Vaccinated macaques demonstrated dramatic decreases in viral RNA in the lungs and nasal swabs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in a golden Syrian hamster model of SARS-CoV-2 infection. Taken together, these results confirm that ChAdTS-S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

Re-Thinking the Role of Government Information Intervention in the COVID-19 Pandemic: An Agent-Based Modeling Analysis

The COVID-19 pandemic imposes new challenges on the capability of governments in intervening with the information dissemination and reducing the risk of infection outbreak. To reveal the complexity behind government intervention decision, we build a bi-layer network diffusion model for the information-disease dynamics that were intervened in and conduct a full space simulation to illustrate the trade-off faced by governments between information disclosing and blocking. The simulation results show that governments prioritize the accuracy of disclosed information over the disclosing speed when there is a high-level medical recognition of the virus and a high public health awareness, while, for the opposite situation, more strict information blocking is preferred. Furthermore, an unaccountable government tends to delay disclosing, a risk-averse government prefers a total blocking, and a low government credibility will discount the effect of information disclosing and aggravate the situation. These findings suggest that information intervention is indispensable for containing the outbreak of infectious disease, but its effectiveness depends on a complicated way on both external social/epidemic factors and the governments’internal preferences and governance capability, for which more thorough investigations are needed in the future.

Reshaping Cell Line Development and CMC Strategy for Fast Responses to Pandemic Outbreak (preprint)

The global pandemic outbreak, SARS-COV-2, which causes COVID-19, has coerced numerous pharmaceutical companies to sprint for the vaccine and therapeutic biologics development. Most of the therapeutic biologics are common human IgG antibodies, which were identified by next-generation sequencing with the B cells from the convalescent patients in less than one-month post-infection. While the global public health emergency calls for medications urgently, it saves lives to expedite the clinical trials of biologics as much as possible, hence the biologics development strategies are unprecedentedly challenged. Since the advent of therapeutic biologics, transfection, and selection strategy has been continuously improving for developing more robust cell lines with greater productivity and efficiency. Next-generation sequencing (NGS) has also been implemented into cell bank testing for acceleration. These recent advances enable us to rethink and reshape the chemistry, manufacturing and controls (CMC) strategy against the pandemic outbreaks, to start supplying cGMP materials for the life-saving clinical trials as soon as possible. We elucidated an accelerated CMC workflow for biologics against pandemics, including using cGMP-compliant pool materials for Phase I clinical trials, selecting the final clone with similar product quality as Phase I materials for late-stage development and commercial production and matching product quality among different manufacturing stages.

A model based on CT radiomic features for predicting RT-PCR becoming negative in coronavirus disease 2019 (COVID-19) patients (preprint)

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic. According to the diagnosis and treatment guidelines of China, negative reverse transcription-polymerase chain reaction (RT-PCR) is the key criterion for discharging COVID-19 patients. However, repeated RT-PCR tests lead to medical waste and prolonged hospital stays for COVID-19 patients during the recovery period. Our purpose is to assess a model based on chest computed tomography (CT) radiomic features and clinical characteristics to predict RT-PCR negativity during clinical treatment. Methods: : From February 10 to March 10, 2020, 203 mild COVID-19 patients in Fangcang Shelter Hospital were retrospectively included (training: n=141; testing: n=62), and clinical characteristics were collected. Lung abnormalities on chest CT images were segmented with a deep learning algorithm. CT quantitative features and radiomic features were automatically extracted. Clinical characteristics and CT quantitative features were compared between RT-PCR-negative and RT-PCR-positive groups. Univariate logistic regression and Spearman correlation analyses identified the strongest features associated with RT-PCR negativity, and a multivariate logistic regression model was established. The diagnostic performance was evaluated for both cohorts. Results: : The RT-PCR-negative group had a longer time interval from symptom onset to CT exams than the RT-PCR-positive group (median 23 vs. 16 days, p<0.001). There was no significant difference in the other clinical characteristics or CT quantitative features. In addition to the time interval from symptom onset to CT exams, nine CT radiomic features were selected for the model. ROC curve analysis revealed AUCs of 0.811 and 0.812 for differentiating the RT-PCR-negative group, with sensitivity/specificity of 0.765/0.625 and 0.784/0.600 in the training and testing datasets, respectively. Conclusion: The model combining CT radiomic features and clinical data helped predict RT-PCR negativity during clinical treatment, indicating the proper time for RT-PCR retesting.

Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies (preprint)

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus virus diseases 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2 infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). In order to understand the mechanism of these nAbs on neutralizing SARS-CoV-2 virus infections, we have performed cryo-EM analysis and here report cryo-EM structures of the ten most potent nAbs in their native full-length IgG or Fab forms bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBD in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and their correlation with more potent neutralization and the shedding of S1 subunit.

The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by CryoEM and CryoET (preprint)

The outbreak of SARS-CoV-2 in December 2019, led to the ongoing global pandemic of coronavirus disease 2019 (COVID‑19), which has claimed more than a half million lives in a few months. Enormous efforts are being made in developing vaccines and therapeutic treatment to fight against COVID-19. Inactivated SARS-CoV-2 viruses are currently used as vaccine candidates; therefore, it is important to understand the architecture of SARS-CoV-2. We have propagated and purified a clinical strain of SARS-CoV-2 and genetically and structurally characterized β-propiolactone inactivated viruses. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are observed, the majority of viral spikes appear nail-shaped resembling a postfusion state, where S1 protein of the spike has disassociated. Cryo-electron tomography and subtomogram averaging of these spikes yielded a density map which closely matches the overall structure of SARS-CoV S2 spike and their corresponding glycosylation sites. Our findings have major implications in SARS-CoV-2 vaccine design owing to the critical importance of prefusion immunogens.Funding: This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality(202002073000002), the National Institutes of Health grant P50AI150481 (P.Z.), the UK Wellcome Trust Investigator Award 206422/Z/17/Z(P.Z.), and the UK Biotechnology and Biological Sciences Research Council grant BB/S003339/1 (P.Z.). Conflict of Interest: The authors declare no competing financial or non-financial interests. Ethical Approval: The research received approval from the Research Ethics Committee of Shenzhen Third People's Hospital, China (approval number: 2020-038). The Research Ethics Committee waived the requirement informed consent before the study started because of the urgent need to collect epidemiological and clinical data. We analyzed the data anonymously.

The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing (preprint)

Understanding the mechanism that leads to immune dysfunction induced by SARS-CoV2 virus is crucial to develop treatment for severe COVID-19. Here, using single cell RNA-seq, we characterized the peripheral blood mononuclear cells (PBMC) from uninfected controls and COVID-19 patients, and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DC) and increased monocytes resembling myeloid-derived suppressor cells (MDSC) which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8+ T cell subsets, compared to health controls. In contrast, the proportions of various activated CD4+ T cell subsets, including Th1, Th2 and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG, TNF, CCL4 and CCL5 etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the patients lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.

Prevalence and risks of severe events for cancer patients with COVID-19 infection: a systematic review and meta-analysis (preprint)

Background The corona virus disease 2019 (COVID-19) pandemic poses a severe challenge to public health, especially to those patients with underlying diseases. In this meta-analysis, we studied the prevalence of cancer among patients with COVID-19 infection and their risks of severe events. Methods We searched the Pubmed, Embase and MedRxiv databases for studies between December 2019 and May 3, 2020 using the following key words and terms: sars-cov-2, covid-19, 2019-ncov, 2019 novel coronavirus, corona virus disease-2019, clinical, clinical characteristics, clinical course, epidemiologic features, epidemiology, and epidemiological characteristics. We extracted data following PICO (patient, intervention, comparison and outcome) chart. Statistical analyses were performed with R Studio (version 3.5.1) on the group-level data. We assessed the studies risk of bias in accordance to the adjusted Joanna Briggs Institute. We estimated the prevalence or risks for severe events including admission into intensive care unit or death using meta-analysis with random effects. Findings Out of the 2,551 studies identified, 32 studies comprising 21,248 participants have confirmed COVID-19. The total prevalence of cancer in COVID-19 patients was 3.97% (95% CI, 3.08% to 5.12%), higher than that of the total cancer rate (0.29%) in China. Stratification analysis showed that the overall cancer prevalence of COVID-19 patients in China was 2.59% (95% CI, 1.72% to 3.90%), and the prevalence reached 3.79% in Wuhan (95% CI, 2.51% to 5.70%) and 2.31% (95% CI, 1.16% to 4.57%) in other areas outside Wuhan in China. The incidence of ICU admission in cancer patients with COVID-19 was 26.80% (95% CI, 21.65% to 32.67%) and the mortality was 24.32% (95% CI, 13.95% to 38.91%), much higher than the overall rates of COVID-19 patients in China. The fatality in COVID patients with cancer was lower than those with cardiovascular disease (OR 0.49; 95% CI, 0.34 to 0.71; p=0.39), but comparable with other comorbidities such as diabetes (OR 1.32; 95% CI, 0.42 to 4.11; p=0.19), hypertension (OR 1.27; 95% CI, 0.35 to 4.62; p=0.13), and respiratory diseases (OR 0.79; 95% CI, 0.47 to 1.33; p=0.45). Interpretation This comprehensive meta-analysis on the largest number of patients to date provides solid evidence that COVID-19 infection significantly and negatively affected the disease course and prognosis of cancer patients. Awareness of this could help guide clinicians and health policy makers in combating cancer in the context of COVID-19 pandemic.

Repurpose Open Data to Discover Therapeutics for COVID-19 using Deep Learning (preprint)

There have been more than 850,000 confirmed cases and over 48,000 deaths from the human coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), in the United States alone. However, there are currently no proven effective medications against COVID-19. Drug repurposing offers a promising way for the development of prevention and treatment strategies for COVID-19. This study reports an integrative, network-based deep learning methodology to identify repurposable drugs for COVID-19 (termed CoV-KGE). Specifically, we built a comprehensive knowledge graph that includes 15 million edges across 39 types of relationships connecting drugs, diseases, genes, pathways, and expressions, from a large scientific corpus of 24 million PubMed publications. Using Amazon AWS computing resources, we identified 41 repurposable drugs (including indomethacin, toremifene and niclosamide) whose therapeutic association with COVID-19 were validated by transcriptomic and proteomic data in SARS-CoV-2 infected human cells and data from ongoing clinical trials. While this study, by no means recommends specific drugs, it demonstrates a powerful deep learning methodology to prioritize existing drugs for further investigation, which holds the potential of accelerating therapeutic development for COVID-19.

Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications (preprint)

IMPORTANCE How to appropriately care for patients who become PCR-negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still not known. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system if a subset were to be PCR-positive again with reactivated SARS-CoV-2. OBJECTIVE To characterize a single center COVID-19 cohort with and without recurrence of PCR positivity, and develop an algorithm to identify patients at high risk of retest positivity after discharge to inform health care policy and case management decision-making. DESIGN, SETTING, AND PARTICIPANTS A cohort of 414 patients with confirmed SARS-CoV-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. EXPOSURES Polymerase chain reaction (PCR) and IgM-IgG antibody confirmed SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Univariable and multivariable statistical analysis of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data to develop an algorithm to predict patients at risk of recurrence of PCR positivity. RESULTS 16.7% (95CI: 13.0%-20.3%) patients retest PCR positive 1 to 3 times after discharge, despite being in strict quarantine. The driving factors in the recurrence prediction model included: age, BMI; lowest levels of the blood laboratory tests during hospitalization for cholinesterase, fibrinogen, albumin, prealbumin, calcium, eGFR, creatinine; highest levels of the blood laboratory tests during hospitalization for total bilirubin, lactate dehydrogenase, alkaline phosphatase; the first test results during hospitalization for partial pressure of oxygen, white blood cell and lymphocyte counts, blood procalcitonin; and the first test episodic Ct value and the lowest Ct value of the nasopharyngeal swab RT PCR results. Area under the ROC curve is 0.786. CONCLUSIONS AND RELEVANCE This case series provides clinical characteristics of COVID-19 patients with recurrent PCR positivity, despite strict quarantine, at a 16.7% rate. Use of a recurrence prediction algorithm may identify patients at high risk of PCR retest positivity of SARS-CoV-2 and help modify COVID-19 case management and health policy approaches.

Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers (preprint)

BackgroundAsymptomatic carriers contribute to the spread of Coronavirus Disease 2019 (COVID-19), but their clinical characteristics, viral kinetics, and antibody responses remain unclear. MethodsA total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. RNA of SARS-CoV-2 was tested using transcriptase quantitative PCR, and the total antibodies (Ab), IgG, IgA and IgM against the SARS-CoV-2 were tested using Chemiluminescence Microparticle Immuno Assay. ResultsAmong 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the communicable period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There was no obvious differences of the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p <0.05). ConclusionYoung COVID-19 patients seem to be asymptomatic cases with early clearance of SARS-CoV-2 and low levels of IgM generation but high total Ab, IgG and IgA. Our findings provide empirical information for viral clearance and antibody kinetics of asymptomatic COVID-19 patients.