Infectious SARS-CoV-2 in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection

Background: SARS-CoV-2 epidemiology implicates airborne transmission; mask source-control efficacy for, variant impact on, and infectiousness of aerosols are not well understood. Methods: We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. Results: We enrolled 61 participants with active infection, May 2020 through April 2021. Among 49 seronegative cases (mean days post onset 3.8 ±2.1), we detected SARS-CoV-2 RNA in 45% of fine (≥5 μm), 31% of coarse (>5 μm) aerosols, and 65% of fomite samples overall and in all samples from four alpha variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, in mid-turbinate swabs, and other potential confounders. Two fine aerosol samples, collected days 2-3 post illness onset, while participants wore masks, were culture-positive. Conclusion: SARS-CoV-2 is evolving toward more efficient airborne transmission and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.

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Evaluation of Viral RNA Recovery Methods in Vectors by Metagenomic Sequencing

Viruses ◽

10.3390/v12050562 ◽

2020 ◽

Vol 12 (5) ◽

pp. 562

Author(s):

Joyce Odeke Akello ◽

Stephen L. Leib ◽

Olivier Engler ◽

Christian Beuret

Keyword(s):

Fold Increase ◽

Extraction Methods ◽

Viral Rna ◽

Health Concern ◽

Metagenomic Sequencing ◽

Optimal Method ◽

Viral Genomes ◽

Tick Borne Encephalitis ◽

Langat Virus ◽

Tick Borne Encephalitis Virus

Identification and characterization of viral genomes in vectors including ticks and mosquitoes positive for pathogens of great public health concern using metagenomic next generation sequencing (mNGS) has challenges. One such challenge is the ability to efficiently recover viral RNA which is typically dependent on sample processing. We evaluated the quantitative effect of six different extraction methods in recovering viral RNA in vectors using negative tick homogenates spiked with serial dilutions of tick-borne encephalitis virus (TBEV) and surrogate Langat virus (LGTV). Evaluation was performed using qPCR and mNGS. Sensitivity and proof of concept of optimal method was tested using naturally positive TBEV tick homogenates and positive dengue, chikungunya, and Zika virus mosquito homogenates. The amount of observed viral genome copies, percentage of mapped reads, and genome coverage varied among different extractions methods. The developed Method 5 gave a 120.8-, 46-, 2.5-, 22.4-, and 9.9-fold increase in the number of viral reads mapping to the expected pathogen in comparison to Method 1, 2, 3, 4, and 6, respectively. Our developed Method 5 termed ROVIV (Recovery of Viruses in Vectors) greatly improved viral RNA recovery and identification in vectors using mNGS. Therefore, it may be a more sensitive method for use in arbovirus surveillance.

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Associations of clinical characteristics and antiviral drugs with viral RNA clearance in patients with COVID-19 in Guangzhou, China: a retrospective cohort study

10.1101/2020.04.09.20058941 ◽

2020 ◽

Cited By ~ 4

Author(s):

Xudan Chen ◽

Yuying Zhang ◽

Baoyi Zhu ◽

Jianwen Zeng ◽

Wenxin Hong ◽

...

Keyword(s):

Clinical Characteristics ◽

Time Lag ◽

Treatment Strategies ◽

Antiviral Drugs ◽

Viral Rna ◽

The Novel ◽

Illness Onset ◽

Treatment Regimens ◽

Global Pandemic ◽

Novel Coronavirus

AbstractBackgroundThe novel coronavirus disease 2019 (COVID-19) characterized by respiratory symptoms has become a global pandemic although factors influencing viral RNA clearance remained unclear to inform optimal isolation period and treatment strategies.MethodsIn this retrospective study, we included patients with confirmed COVID-19 admitted to Guangzhou Eighth People’s Hospital from 20th January 2020 to 15th March 2020. The associations of clinical characteristics and treatment regimens on time to viral RNA clearance were analyzed.ResultsWe examined 284 consecutive COVID-19 cases, accounting for 82% of confirmed cases in Guangzhou during this period. At the time of reporting (20th March 2020), 276 (97.2%) had recovered and were discharged from hospital with a median hospital stay of 18 days (interquartile range [IQR]:13-24). Overall, 280 patients achieved viral RNA clearance with a median length of 12 days (IQR: 8-16) after onset of illness. Amongst them, 66.1% had viral RNA cleared within 14 days, and 89.3% within 21 days. Older age, severity of disease, time lag from illness onset to hospital admission, high body temperature, and corticosteroid use were associated with delayed clearance of viral RNA. None of the antiviral regimens (chloroquine, oseltamivir, arbidol, and lopinavir/ritonavir) improved viral RNA clearance. The use of lopinavir/ritonavir was associated with delayed clearance of viral RNA after adjusting for confounders.ConclusionIn patients with COVID-19, isolation for a minimum of 21 days after onset of illness may be warranted, while the use of antiviral drugs does not enhance viral RNA clearance.Brief SummaryViral RNA was cleared in 89% of the COVID-19 patients within 21 days after illness onset. The use of antiviral drugs (chloroquine, oseltamivir, arbidol, and lopinavir/ritonavir) did not shorten viral RNA clearance, especially in non-serious cases.

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Antibiotic Resistance of Human Periodontal Pathogen Parvimonas micra Over 10 Years

Antibiotics ◽

10.3390/antibiotics9100709 ◽

2020 ◽

Vol 9 (10) ◽

pp. 709

Author(s):

Thomas E. Rams ◽

Jacqueline D. Sautter ◽

Arie J. van Winkelhoff

Keyword(s):

United States ◽

Fold Increase ◽

Periodontal Pathogen ◽

Antibiotic Concentration ◽

P Values ◽

Parvimonas Micra ◽

Severe Periodontitis ◽

Patient Groups ◽

Culture Positive

Changes were evaluated over 10 years in the in vitro resistance of human periodontopathic strains of Parvimonas micra to four antibiotics. Subgingival biofilms culture positive for P. micra from 300 United States adults with severe periodontitis in 2006, and from a similar group of 300 patients in 2016, were plated onto anaerobically incubated enriched Brucella blood agar alone, or supplemented with either doxycycline (4 mg/L), clindamycin (4 mg/L), amoxicillin (8 mg/L), or metronidazole (16 mg/L). P. micra growth on antibiotic-supplemented media indicated in vitro resistance to the evaluated antibiotic concentration. P. micra resistance was significantly more frequent among patients in 2016, as compared to 2006, for doxycycline (11.3% vs. 0.3% patients; 37.7-fold increase), and clindamycin (47.3% vs. 2.0% patients; 23.7-fold increase) (both p < 0.001), whereas resistance to amoxicillin (2.3% vs. 1.0% patients) and metronidazole (0% vs. 0.3% patients) remained low and statistically unchanged between the two patient groups (p-values > 0.05). No P. micra isolates in 2006 or 2016 were jointly resistant in vitro to both amoxicillin and metronidazole. The alarming increases in subgingival P. micra resistance to doxycycline and clindamycin raise serious questions about the empiric use of these antibiotics, either locally or systemically, in the treatment of United States periodontitis patients harboring subgingival P. micra.

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Detection of Anti-Nucleocapsid Antibody in COVID-19 Patients in Bangladesh Is not Correlated with Previous Dengue Infection

Pathogens ◽

10.3390/pathogens10060637 ◽

2021 ◽

Vol 10 (6) ◽

pp. 637

Author(s):

Simon D. Lytton ◽

Mahmuda Yeasmin ◽

Asish Kumar Ghosh ◽

Md. Rakibul Hassan Bulbul ◽

Md. Maruf Ahmed Molla ◽

...

Keyword(s):

Dengue Infection ◽

Antibody Responses ◽

Viral Rna ◽

Structural Protein ◽

Rt Pcr ◽

Chain Reaction ◽

N Protein ◽

Polymerase Chain ◽

Normal Controls ◽

Post Onset

Background: The assessment of antibody responses to severe acute respiratory syndrome coronavirus-2 is potentially confounded by exposures to flaviviruses. The aims of the present research were to determine whether anti-dengue antibodies affect the viral load and the detection of anti-coronavirus nucleocapsid (N)-protein antibodies in coronavirus infectious disease 2019 (COVID-19) in Bangladesh. Methods: Viral RNA was evaluated in swab specimens from 115 COVID-19 patients by real-time reverse transcription polymerase chain reaction (rT-PCR). The anti-N-protein antibodies, anti-dengue virus E-protein antibodies and the dengue non-structural protein-1 were determined in serum from 115 COVID-19 patients, 30 acute dengue fever pre-COVID-19 pandemic and nine normal controls by ELISA. Results: The concentrations of viral RNA in the nasopharyngeal; Ct median (95% CI); 22 (21.9–23.3) was significantly higher than viral RNA concentrations in oropharyngeal swabs; and 29 (27–30.5) p < 0.0001. Viral RNA concentrations were not correlated with-dengue IgG levels. The anti-nucleocapsid antibodies were IgA 27% positive and IgG 35% positive at days 1 to 8 post-onset of COVID-19 symptoms versus IgA 0% and IgG 0% in dengue patients, p < 0.0001. The levels of anti- nucleocapsid IgA or IgG versus the levels of anti-dengue IgM or IgG revealed no significant correlations. Conclusions: Viral RNA and anti-nucleocapsid antibodies were detected in COVID-19 patients from dengue-endemic regions of Bangladesh, independently of the dengue IgG levels.

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Evaluation of a genus-specific rGroEL1-524 IgM-ELISA and commercial ELISA kits during the course of leptospirosis in Thailand

Scientific Reports ◽

10.1038/s41598-021-99377-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Santi Maneewatchararangsri ◽

Galayanee Doungchawee ◽

Thareerat Kalambaheti ◽

Viravarn Luvira ◽

Ngamphol Soonthornworasiri ◽

...

Keyword(s):

Early Diagnosis ◽

Screening Test ◽

Scrub Typhus ◽

Acute Infection ◽

Febrile Illness ◽

High Sensitivity ◽

Elisa Assay ◽

Igm Elisa ◽

Culture Positive ◽

Post Onset

AbstractIn the present study, we developed a genus-specific rGroEL1-524 IgM-ELISA assay for use in screening diagnosis of suspected leptospirosis among acute undifferentiated febrile illness patients during acute fever. The diagnostic accuracies of the rGroEL1–524 IgM-ELISA, commercial Panbio IgM-ELISA, and Virion-Serion Classic IgG-ELISA were evaluated using 133 Thai leptospirosis sera and 210 controls. Sensitivities were 91.7%, 59.6%, and 17.7% for acute infection, and the specificities were 92.6%, 90.2%, and 88.3% for the non-leptospirosis control, respectively. The rGroEL1-524 IgM-ELISA had high sensitivity, at 92.3% and 91.7%, among culture-positive and MAT-negative cases at 1–3 days post-onset of symptoms (DPO1–3), respectively. Impaired specificity on scrub typhus was found, possibly from antibody cross-reaction to ortholog GroEL. Commercial Panbio IgM-ELISA had sensitivities at DPO1–3 of 30.8% and 41.7% for culture-positive and MAT-negative cases whereas Virion-Serion IgG-ELISA showed sensitivities of 5.9% and 13.3%, respectively. The rGroEL1-524 IgM-ELISA could be useful as a screening test for early diagnosis. The performance of the commercial ELISA suggests the applicability of IgM-ELISA for diagnosis, while IgG-ELISA is useful for seroprevalence surveys. However, confirmation by reference tests is recommended.

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Anatomy of the first six months of COVID-19 Vaccination Campaign in Italy

10.1101/2021.11.24.21266820 ◽

2021 ◽

Author(s):

Nicolò Gozzi ◽

Matteo Chinazzi ◽

Jessica T. Davis ◽

Kunpeng Mu ◽

Ana Pastore y Piontti ◽

...

Keyword(s):

Vaccination Campaign ◽

Age Groups ◽

Modeling Framework ◽

Frontline Workers ◽

Vaccination Rates ◽

Time Period ◽

Alpha Variant ◽

Vaccination Campaigns ◽

Allocation Strategies

We analyze the effectiveness of the first six months of vaccination campaign against SARS-CoV-2 in Italy by using a computational epidemic model which takes into account demographic, mobility, vaccines, as well as estimates of the introduction and spreading of the more transmissible Alpha variant. We consider six sub-national regions and study the effect of vaccines in terms of number of averted deaths, infections, and reduction in the Infection Fatality Rate (IFR) with respect to counterfactual scenarios with the actual non-pharmaceuticals interventions but no vaccine administration. Furthermore, we compare the effectiveness in counterfactual scenarios with different vaccines allocation strategies and vaccination rates. Our results show that, as of 2021/07/05, vaccines averted 29,350 (IQR: [16,454-42,826]) deaths and 4,256,332 (IQR: [1,675,564-6,980,070]) infections and a new pandemic wave in the country. During the same period, they achieved a -22.2% (IQR: [-31.4%; -13.9%]) reduction in the IFR. We show that a campaign that would have strictly prioritized age groups at higher risk of dying from COVID-19, besides frontline workers, would have implied additional benefits both in terms of avoided fatalities and reduction in the IFR. Strategies targeting the most active age groups would have prevented a higher number of infections but would have been associated with more deaths. Finally, we study the effects of different vaccination intake scenarios by rescaling the number of available doses in the time period under study to those administered in other countries of reference. The modeling framework can be applied to other countries to provide a mechanistic characterization of vaccination campaigns worldwide.

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Increased aerosol transmission for B.1.1.7 (alpha variant) over lineage A variant of SARS-CoV-2

10.1101/2021.07.26.453518 ◽

2021 ◽

Author(s):

Julia Port ◽

Kwe Claude Yinda ◽

Victoria Avanzato ◽

Jonathan Schulz ◽

Myndi Holbrook ◽

...

Keyword(s):

Transmission Efficiency ◽

Mitigation Strategies ◽

Transmission Route ◽

Airborne Transmission ◽

Experimental Proof ◽

Infectious Dose ◽

Successful Transmission ◽

Transmission Potential ◽

Novel Variants ◽

Alpha Variant

Airborne transmission, a term combining both large droplet and aerosol transmission, is thought to be the main transmission route of SARS-CoV-2. Here we investigated the relative efficiency of aerosol transmission of two variants of SARS-CoV-2, B.1.1.7 (alpha) and lineage A, in the Syrian hamster. A novel transmission caging setup was designed and validated, which allowed the assessment of transmission efficiency at various distances. At 2 meters distance, only particles <5 micrometer traversed between cages. In this setup, aerosol transmission was confirmed in 8 out of 8 (N = 4 for each variant) sentinels after 24 hours of exposure as demonstrated by respiratory shedding and seroconversion. Successful transmission occurred even when exposure time was limited to one hour, highlighting the efficiency of this transmission route. Interestingly, the B.1.1.7 variant outcompeted the lineage A variant in an airborne transmission chain after mixed infection of donors. Combined, this data indicates that the infectious dose of B.1.1.7 required for successful transmission may be lower than that of lineage A virus. The experimental proof for true aerosol transmission and the increase in the aerosol transmission potential of B.1.1.7 underscore the continuous need for assessment of novel variants and the development or preemptive transmission mitigation strategies.

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The source control effect of personal protection equipment and physical barrier on short-range airborne transmission

Building and Environment ◽

10.1016/j.buildenv.2022.108751 ◽

2022 ◽

pp. 108751

Author(s):

Chen Zhang ◽

Peter V. Nielsen ◽

Li Liu ◽

Emilie Tranegaard Sigmer ◽

Sarah Ghoreishi Mikkelsen ◽

...

Keyword(s):

Short Range ◽

Source Control ◽

Personal Protection ◽

Physical Barrier ◽

Control Effect ◽

Airborne Transmission ◽

Personal Protection Equipment

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Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season

10.1101/439471 ◽

2018 ◽

Author(s):

Min Z. Levine ◽

Emily T. Martin ◽

Joshua G. Petrie ◽

Adam S. Lauring ◽

Crystal Holiday ◽

...

Keyword(s):

Hong Kong ◽

Influenza A ◽

Geometric Mean ◽

Fold Increase ◽

Vaccine Effectiveness ◽

Similar Increase ◽

Illness Onset ◽

Antibody Titers ◽

H3n2 Vaccine ◽

Independent Effects

ABSTRACTBackgroundThe 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.MethodsSerum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.ResultsMN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.ConclusionAlthough individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.

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Molecular and serological investigation of the 2021 COVID-19 case surge in Mongolian vaccinees

10.1101/2021.08.11.21261915 ◽

2021 ◽

Author(s):

Naranjargal J. Dashdorj ◽

Naranbaatar D. Dashdorj ◽

Mitali Mishra ◽

Lisa Danzig ◽

Thomas Briese ◽

...

Keyword(s):

Sequence Analysis ◽

Nasal Swab ◽

Spike Protein ◽

Vaccine Failure ◽

Vaccination Rates ◽

Serological Investigation ◽

Antibody Assays ◽

Virus Sequence ◽

Alpha Variant

A surge in Covid-19 cases in Mongolia in March 2021 resulted in a government-mandated shutdown. This shutdown was relaxed in May 2021 as case numbers decreased and nationwide vaccination rates using Sinopharm, Covishield/AstraZeneca, Sputnik V, and Pfizer/BioNTech vaccines exceeded 50% of the population. Case rates increased again in early June 2021 in both vaccinated and non-vaccinated individuals. To determine whether the surge was due to the emergence of Delta or another variant, or vaccine failure, a rapid, opportunistic investigation was conducted that comprised virus sequence analysis of nasal swab samples from breakthrough cases and antibody assays of plasma from healthy vaccinees. More than 90% of breakthrough infections during the second case surge were due to the Alpha variant. Spike protein ELISA and SARS-CoV-2 neutralization assays data revealed large differences in plasma titers of antibodies to SARS-CoV-2, with mRNA vaccines eliciting higher titers than adenovirus-vectored or killed virus vaccines.

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