ABSTRACT
Messenger RNA（mRNA） vaccine, with antigen-encoded mRNA packaged in delivery vehicles, performs its functions via antigen translation and specific immune response. mRNA vaccines have proven their protective effects and safety in the ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）. The World Health Organization issued guidelines specifically for prophylactic mRNA vaccines in 2021, which provide important guidance for non-clinical research on mRNA vaccines. Furthermore, some unusual adverse reactions, such as cerebrovascular disease, embolic stroke, transient cerebral ischemia, deep vein thrombosis, myocarditis（pericarditis） and allergic reactions, have been also found in clinical trials and applications of mRNA vaccines, which deserves attention in non-clinical studies.
ABSTRACT
Background: More than 210,000 medical workers have fought against the Coronavirus Disease 2019 (COVID-19) in Hubei of China since December 2019. However, it was unknown if the mental health disorders for frontline medical staff was relieved one month later. Methods: Medical workers in Wuhan and other cities in Hubei Province was requested to fill out an online survey, which assessed their degrees of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). Outcomes: A total of 1,091 respondents (32·63% male, 67·37% female) were valid for statistical analysis. The prevalence was anxiety (52·98% with male 50·84% and female 54·01%), insomnia (78·83% with male 78·09% and female 79·18%), depression (56·10% with male 55·34% and female 56·46%) and PTSD (11·09% with male 10·11% and female 11·56%). For educational attainment, those with doctoral and masters’ degrees (D/M) may suffer from more anxiety (median 7·0 [IQR 2·0-8·5] vs. median 5·0 [IQR 5·0-8·0], P =0·02) and PTSD (median 26·0 [IQR 19·5-33·0] vs. median 23·0 [IQR 19·0-31·0], P =0·04) than those with lower educational degrees. Interpretation: Mental disorders of healthcare workers were little relieved one month after they had ended fighting COVID-19, and potential mitigating factors and interventions is necessary.Funding Statement: The study was financially supported by the National Natural Science Foundation of China (8174356); the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) (WDCM2018002); the Key Discipline Project of Hubei University of Medicine and the Foundation for Innovative Research Team of Hubei University of Medicine (2018YHKT01).Declaration of Interests: The authors declared no interest conflict in this study.Ethics Approval Statement: This study was approved by the Ethic Committee of Renmin Hospital of Hubei University of Medicine.
Subject(s)
COVID-19 , Anxiety Disorders , Mental Disorders , Stress Disorders, Post-TraumaticABSTRACT
COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cfDNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation. This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.
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COVID-19ABSTRACT
We report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors. We additionally describe the longitudinal dynamics of immunoglobulin-G, immunoglobulin-M, and in vitro neutralizing antibody titers in COVID-19 patients. Neutralizing antibodies rise in tandem with immunoglobulin levels following symptom onset, exhibiting median time to seroconversion within one day of each other, and there is >93% positive percent agreement between detection of immunoglobulin-G and neutralizing titers.
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COVID-19ABSTRACT
Serologic assays are needed to determine SARS-CoV-2 seroprevalence, but poor specificity can overestimate exposures. Here, we built a pan-human coronavirus proteome-wide programmable phage display assay (VirScan) to profile coronavirus antigens specifically enriched by 20 COVID-19 patient serum IgG. With ReScan, a new diagnostic development workflow which combines the isolation of phage expressing the most immunogenic peptides with paper-based microarrays manufactured via acoustic liquid handling, we identified 9 candidate antigens from a library of 534 SARS-CoV-2 peptides. These arrays could form the basis of a multiplexed COVID-19 serologic assay with enhanced specificity. ReScan has broad applicability for serologic assay development.
Subject(s)
COVID-19ABSTRACT
Background Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. Method We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. Results Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7-94.8%. No consistent cross-reactivity was observed. Conclusion Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.
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COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Real-time dissemination of epidemiological survey data from positive COVID-19 cases is critical to support efforts to contain or reduce spread of viral infection in the community. Here we detected a significant association between domestic travel or travel to Europe and the identification of new cases in San Francisco, California, USA. These findings suggest that domestic and European travelers may need to be prioritized for evaluation of acute infection from COVID-19 in the setting of limited testing capacity.
Subject(s)
COVID-19 , Virus DiseasesABSTRACT
Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19 , InfectionsABSTRACT
The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.
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COVID-19ABSTRACT
Background: To investigate the correlations between serum calcium and clinical severity and outcomes in patients with coronavirus disease 2019 (COVID-19).Methods: In this clinical retrospective study, the levels of serum calcium, hormone levels and clinical laboratory parameters of admission were recorded. The clinical severity and outcome variables were also recorded.Results: From February 10 to February 28 2020, 241 patients were enrolled in this study. Of these patients, 180 (74.7%) had hypocalcemia on admission. The median serum calcium levels were 2.12 (IQR, 2.04-2.20) mmol/L, median parathyroid hormone (PTH) levels were 55.27 (IQR, 42.73-73.15) pg/mL, median 25-hydroxy-vitamin D (VD) levels were 10.20 (IQR, 8.20-12.65) ng/mL. The serum calcium levels were significantly positive correlated with VD levels (P =0.004), whereas negative correlated with PTH levels (P = 0.048). Patients with lower serum calcium levels (especially ≤2.0 mmol/L) had worse clinical parameters, higher incidence of organ injury septic shock and higher 28-day mortality. The areas under the receiver operating characteristic curves of multiple organ dysfunction syndrome, septic shock, and 28-day mortality were 0.923 (P <0.001), 0.905 (P =0.001), and 0.929 (P <0.001), respectively. The overall mortality of COVID-19 was 4.1% (10/241), whereas the mortality of critical patients was up to 40.0% (10/25). Conclusions: Serum calcium was associated with clinical severity and prognosis of patients with COVID-19. Hypocalcemia may be associated with imbalanced VD and PTH.
Subject(s)
Multiple Organ Failure , Shock, Septic , Hypocalcemia , COVID-19 , Vitamin D DeficiencyABSTRACT
An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (~30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.