COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Research Article
Comparison of the Clinical Performance of the Abbott Alinity IgG, Abbott Architect IgM, and Roche Elecsys Total SARS-CoV-2 Antibody Assays
Critical evaluation of SARS-CoV-2 serologic assays is needed to guide clinical decision-making and ensure these assays provide optimal benefit to patients and the public. Here, three commercially available assays with widespread distribution capabilities are compared. A total of 667 specimens, 103 from patients with confirmed SARS-CoV-2 infections and 564 collected prior to the emergence of SARS-CoV-2, were analyzed in parallel using the Roche Elecsys SARS-CoV-2 Total Antibody and Abbott Alinity SARS-CoV-2 IgG assays; a subset of 55 samples from patients with confirmed SARS-CoV-2 infections was additionally evaluated using the Abbott Architect SARS-CoV-2 IgM assay. Qualitative percent agreement between the Abbott IgG and Roche total antibody assays was 98.7% (658/667), with Cohen's kappa 0.919 (95% CI 0.867-0.972). Qualitative percent agreement with the Abbott IgM assay was 92.7% (51/55, Abbott IgG) and 85.5% (47/55, Roche total antibody). Diagnostic specificities determined using pre-COVID-19 samples for the Abbott IgG and Roche total antibody assays were 99.65% (95% CI 98.72-99.90%) and 100.00% (95% CI 99.32-100.00%), respectively, spanning claims made by each manufacturer. Diagnostic sensitivities increased for all three assays with increasing time since the onset of symptoms. Among 51 patients with confirmed SARS-CoV-2 infections, 23 (45.1%), 24 (47.1%), and 22 (43.1%) were reactive by the Abbott IgG, Roche total antibody, and Abbott IgM assays, respectively, with sampling times 0-56 days post-positive PCR (median/mean 2/6.2 days). Combining IgG and IgM screening identified 4/55 additional samples with detectable antibodies that would not have been observed using the assays independently. Notably, one immunocompromised patient with confirmed SARS-CoV-2 infection showed no detectable antibodies using any of the three assays 43 days after onset of symptoms.
Accepted Manuscript Posted 26 October 2020, JCM; Final Article Posted 17 December 2020
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Research Article
The Interaction of Natural and Vaccine-Induced Immunity with Social Distancing Predicts the Evolution of the COVID-19 Pandemic
The ability of our society to function effectively moving forward will depend on how the spread of the SARS-CoV-2 virus is contained. Immunity to the virus will be critical to this equation.
23 October 2020, mBio
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Research Article
Comparison of upper respiratory viral load distributions in asymptomatic and symptomatic children diagnosed with SARS-CoV-2 infection in pediatric hospital testing programs
The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with SARS-CoV-2 is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay, and converted to estimated VL (copies/mL) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 vs. 197 ages 0-4; 79 vs 97 ages 5-9; 69 vs 75 ages 10-13; 73 vs 109 ages 14-17) were compared. The median adjusted Ct value in asymptomatic children was 10.3 cycles higher than for symptomatic children (p< 0.0001), and VL 3-4 logs lower (p<0.0001); differences were consistent (p<0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (OR 6.5, p = 0.01), recent contact (OR 2.3, p = 0.02), and testing for surveillance (OR 2.7, p = 0.005) had higher estimated risk of having a Ct value in the lowest quartile than children without, while immunocompromise had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in the nasopharynx/oropharynx than symptomatic children, but timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.
Accepted Manuscript Posted 22 October 2020, JCM; Final Article Posted 17 December 2020
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Genome Sequences
Coding-Complete Genome Sequences of 23 SARS-CoV-2 Samples from the Philippines
Here, we report the coding-complete genome sequences of 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples from the Philippines. Sequences were obtained from nasopharyngeal and oropharyngeal swabs from coronavirus disease 2019 (COVID-19)-positive patients. Mutation analysis showed the presence of the D614G mutation in the spike protein in 22 of 23 genomes.
22 October 2020, MRA
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Research Article
COVID-19 associated invasive aspergillosis: data from the UK National Mycology Reference Laboratory
COVID-19 associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following SARS-CoV-2 infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardised diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11th March and 14th July 2020, the UK National Mycology Reference Laboratory received 1267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1000 (1-3)-β-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavages, tracheal aspirates, sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus-specific PCR and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA especially when only limited clinical samples are available for testing, and the importance of a multi-modal diagnostic approach involving regular and repeat testing of both serum and respiratory samples.
Accepted Manuscript Posted 21 October 2020, JCM; Final Article Posted 17 December 2020
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Letter to the Editor
Combined Self-collected Anterior Nasal and Oropharyngeal Specimens versus Provider-collected Nasopharyngeal Swabs for the Detection of SARS-CoV-2
The U.S. Food and Drug Administration (FDA) guidance and Centers for Disease Control interim guidelines for SARS-CoV-2 testing lists patient self-collected anterior nares swab (ANS) as an acceptable alternative to the standard healthcare provider (HCP)-collected nasopharyngeal swab (NPS).…
Accepted Manuscript Posted 21 October 2020, JCM; Final Article Posted 17 December 2020
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Research Article
Humidity and Deposition Solution Play a Critical Role in Virus Inactivation by Heat Treatment of N95 Respirators
Shortages of personal protective equipment, including N95 respirators, during the coronavirus (CoV) disease 2019 (COVID-19) pandemic have highlighted the need to develop effective decontamination strategies for their reuse. This is particularly important in health care settings for reducing exposure to respiratory viruses, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Although several treatment methods are available, a widely accessible strategy will be necessary to combat shortages on a global scale. We demonstrate that the combination of heat and humidity inactivates a range of RNA viruses, including both viral pathogens and common viral pathogen surrogates, after deposition on N95 respirators and achieves the necessary virus inactivation detailed by the U.S. Food and Drug Administration guidelines to validate N95 respirator decontamination technologies. We further demonstrate that depositing viruses onto surfaces when suspended in culture media can greatly enhance observed inactivation, adding caution to how heat and humidity treatment methods are validated.
21 October 2020, mSphere
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Observation
Effectiveness of Face Masks in Preventing Airborne Transmission of SARS-CoV-2
Airborne simulation experiments showed that cotton masks, surgical masks, and N95 masks provide some protection from the transmission of infective SARS-CoV-2 droplets/aerosols; however, medical masks (surgical masks and even N95 masks) could not completely block the transmission of virus droplets/aerosols even when sealed.
21 October 2020, mSphere
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Research Article
Inhibition of Coronavirus Entry In Vitro and Ex Vivo by a Lipid-Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain
SARS-CoV-2, the causative agent of COVID-19, continues to spread globally, placing strain on health care systems and resulting in rapidly increasing numbers of cases and mortalities. Despite the growing need for medical intervention, no FDA-approved vaccines are yet available, and treatment has been limited to supportive therapy for the alleviation of symptoms. Entry inhibitors could fill the important role of preventing initial infection and preventing spread. Here, we describe the design, synthesis, and evaluation of a lipopeptide that is derived from the HRC domain of the SARS-CoV-2 S glycoprotein that potently inhibits fusion mediated by SARS-CoV-2 S glycoprotein and blocks infection by live SARS-CoV-2 in both cell monolayers (in vitro) and human airway tissues (ex vivo). Our results highlight the SARS-CoV-2 HRC-derived lipopeptide as a promising therapeutic candidate for SARS-CoV-2 infections.
20 October 2020, mBio
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Research Article
Accurate Diagnosis of COVID-19 by a Novel Immunogenic Secreted SARS-CoV-2 orf8 Protein
Current commercially available serological tests for COVID-19 patients are detecting antibodies against SARS-CoV-2 nucleoprotein and spike glycoprotein. The antinucleoprotein and antispike antibodies can be accurately detected in patients during the mid or late stage of infection, and therefore, these assays have not been widely used for early diagnosis of COVID-19. In this study, we characterized the secretory property of a SARS-CoV-2 orf8 protein and proposed that orf8 secretion during infection facilitates early mounting of the B cell response. We demonstrated the presence of anti-orf8 antibodies in both symptomatic and asymptomatic patients during the early stage of infection, while the anti-N antibody is not detected. Our serological test detecting anti-orf8 antibodies may facilitate the development of early and accurate diagnosis for COVID-19.
20 October 2020, mBio
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Research Article
Metagenomic sequencing to detect respiratory viruses in persons under investigation for COVID-19
Broad testing for respiratory viruses among persons under investigation (PUIs) for SARS-CoV-2 has been performed inconsistently, limiting our understanding of alternative viral infections and co-infections in these patients. RNA metagenomic next-generation sequencing (mNGS) offers an agnostic tool for the detection of both SARS-CoV-2 and other RNA respiratory viruses in PUIs. Herein, we used RNA mNGS to assess the frequencies of alternative viral infections in SARS-CoV-2 RT-PCR negative PUIs (n=30) and viral co-infections in SARS-CoV-2 RT-PCR positive PUIs (n=45). mNGS identified all viruses detected by routine clinical testing (Influenza A (N=3), Human metapneumovirus (N=2), Human coronavirus OC43 (N=2) and Human coronavirus HKU1(N=1)). mNGS also identified both co-infections (1, 2.2%) and alternative viral infections (4, 13.3%) that were not detected by routine clinical workup (Respiratory syncytial virus (N=3), Human metapneumovirus (N=1), Human coronavirus NL63 (N=1)). Among SARS-CoV-2 RT-PCR positive PUIs, lower cycle threshold (CT) values correlated with greater SARS-CoV-2 read recovery by mNGS (R2: 0.65, p-value: <0.001). Our results suggest that current broad-spectrum molecular testing algorithms identify most respiratory viral infections among SARS-CoV-2 PUIs, when available and implemented consistently.
Accepted Manuscript Posted 16 October 2020, JCM; Final Article Posted 17 December 2020
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Research Article
COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva
SARS-CoV-2 is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a non-invasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed COVID-19 cases and from the pre-COVID-19 era were tested for IgG, IgA and IgM to the antigen panel. Matched saliva and serum IgG responses (n=28) were significantly correlated. The salivary anti-N IgG response resulted in highest sensitivity (100%), exhibiting a positive response in 24/24 RT-PCR-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert around 10 DPSO. Algorithms employing a combination of the IgG response to N and S antigens result in high diagnostic accuracy (100%) as early as 10 DPSO. These results support the use of saliva-based antibody testing as a non-invasive and scalable alternative to blood-based antibody testing.
Accepted Manuscript Posted 16 October 2020, JCM; Final Article Posted 17 December 2020
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Letter to the Editor
Identification of a polymorphism in the N gene of SARS-CoV-2 that adversely impacts detection by RT-PCR
Since April 7, 2020, our COVID-19 diagnostic laboratory (CLIAHUB) has received samples from multiple counties in California — our RT-PCR protocol (1) employs N-gene (NIID_2019-nCov_N_F2/R2ver3/P2 (Japan) (2)) and E-gene (E_Sarbeco_F/R/P1 (Germany) (3)) simplex assays.…
Accepted Manuscript Posted 16 October 2020, JCM; Final Article Posted 17 December 2020
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Research Article
SARS-CoV-2 Is Restricted by Zinc Finger Antiviral Protein despite Preadaptation to the Low-CpG Environment in Humans
Although interferons inhibit SARS-CoV-2 and have been evaluated for treatment of coronavirus disease 2019 (COVID-19), the most effective types and antiviral effectors remain to be defined. Here, we show that IFN-γ is particularly potent in restricting SARS-CoV-2 and in inducing expression of the antiviral factor ZAP in human lung cells. Knockdown experiments revealed that endogenous ZAP significantly restricts SARS-CoV-2. We further show that CpG dinucleotides which are specifically targeted by ZAP are strongly suppressed in the SARS-CoV-2 genome and that the two closest horseshoe bat relatives of SARS-CoV-2 show the lowest genomic CpG content of all coronavirus sequences available from this reservoir host. Nonetheless, both the short and long isoforms of human ZAP reduced SARS-CoV-2 RNA levels, and this activity was conserved in horseshoe bat and pangolin ZAP orthologues. Our findings indicating that type II interferon is particularly efficient against SARS-CoV-2 and that ZAP restricts this pandemic viral pathogen might promote the development of effective immune therapies against COVID-19.
16 October 2020, mBio
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Observation
Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals
While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.
16 October 2020, mBio