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1.
Nature Communications ; 13(1):2451-2451, 2022.
Article in English | PMC | ID: covidwho-1821584

ABSTRACT

As SARS-CoV-2 continues to spread and vaccines are rolled-out, the “double burden” of disparities in exposure and vaccination intersect to determine patterns of infection, immunity, and mortality. Serology provides a unique opportunity to measure prior infection and vaccination simultaneously. Leveraging algorithmically-selected residual sera from two hospital networks in the city of San Francisco, cross-sectional samples from 1,014 individuals from February 4–17, 2021 were each tested on two assays (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 and Roche Elecsys Anti-SARS-CoV-2), capturing the first year of the epidemic and early roll-out of vaccination. We estimated, using Bayesian estimation of infection and vaccination, that infection risk of Hispanic/Latinx residents was five times greater than of White residents aged 18–64 (95% Credible Interval (CrI): 3.2–10.3), and that White residents over 65 were twice as likely to be vaccinated as Black/African American residents (95% CrI: 1.1–4.6). We found that socioeconomically-deprived zipcodes had higher infection probabilities and lower vaccination coverage than wealthier zipcodes. While vaccination has created a ‘light at the end of the tunnel’ for this pandemic, ongoing challenges in achieving and maintaining equity must also be considered.

2.
Cell Reports Medicine ; : 100640, 2022.
Article in English | ScienceDirect | ID: covidwho-1819630

ABSTRACT

Summary SARS-CoV-2-specific CD4+ T cells are likely important in immunity against COVID-19, but our understanding of CD4+ longitudinal dynamics following infection, and specific features that correlate with the maintenance of neutralizing antibodies, remains limited. Here, we characterize SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4+ response shifts from cells producing IFNγ to TNFα from five days to four months post-enrollment, with IFNγ-IL21-TNFα+ CD4+ T cells the predominant population detected at later timepoints. Greater percentages of IFNγ-IL21-TNFα+ CD4+ T cells on day 28 correlate with SARS-CoV-2 neutralizing antibodies measured seven months post-infection (⍴=0.4, P=0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ and TNFα producing, spike protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNFα-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.

3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328540

ABSTRACT

The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial in SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We identify early immune signatures, including plasma RIG-I levels, early interferon signaling, and related cytokines (CXCL10, MCP1, MCP-2 and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2 specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizer–BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine learning models using 7-10 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.

4.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327766

ABSTRACT

Five years of sustained indoor residual spraying (IRS) of insecticide from 2014 to 2019, first using a carbamate followed by an organophosphate, was associated with a marked reduction in the burden of malaria in five districts of Uganda. We assessed malaria burden over an additional 21 months, corresponding to a change in IRS formulations using clothianidin with and without deltamethrin and the start of the COVID-19 pandemic. We document an unprecedented resurgence in malaria burden: in years 4-5 of sustained IRS cases were 84% lower than the pre-IRS period, in year 6 this increased to a 43% reduction, and in the first 9 months of year 7, cases were 39% higher than pre-IRS levels. The timing of this resurgence corresponded to a change of active ingredient to clothianidin, a new IRS active ingredient. Further research is needed to determine mechanisms leading to this resurgence.

5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327138

ABSTRACT

SARS–CoV–2–specific CD4 + T cells are likely important in immunity against COVID–19, but our understanding of CD4 + longitudinal dynamics following infection, and specific features that correlate with the maintenance of neutralizing antibodies, remains limited. We characterized SARS–CoV–2–specific CD4 + T cells in a longitudinal cohort of 109 COVID–19 outpatients. The quality of the SARS–CoV–2–specific CD4 + response shifted from cells producing IFNγ to TNFα from five days to four months post–enrollment, with IFNγ − IL21 − TNFα + CD4 + T cells the predominant population detected at later timepoints. Greater percentages of IFNγ − IL21 − TNFα + CD4 + T cells on day 28 correlated with SARS–CoV–2 neutralizing antibodies measured seven months post–infection (ρ=0.4, P=0.01). mRNA vaccination following SARS–CoV–2 infection boosted both IFNγ and TNFα producing, spike protein–specific CD4 + T cells. These data suggest that SARS–CoV–2–specific, TNFα–producing CD4 + T cells may play an important role in antibody maintenance following COVID–19.

6.
Open Forum Infect Dis ; 9(2): ofab640, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1672244

ABSTRACT

Background: There is mounting evidence for the presence of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), but there is limited information on the spectrum, magnitude, duration, and patterns of these sequelae as well as their influence on quality of life. Methods: We assembled a cohort of adults with a documented history of SARS-CoV-2 RNA positivity at ≥2 weeks past onset of coronavirus disease 2019 (COVID-19) symptoms or, if asymptomatic, first positive test. At 4-month intervals, we queried physical and mental health symptoms and quality of life. Results: Of the first 179 participants enrolled, 10 were asymptomatic during the acute phase of SARS-CoV-2 infection, 125 were symptomatic but not hospitalized, and 44 were symptomatic and hospitalized. During the postacute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping, and anosmia/dysgeusia were most common through 8 months of observation. Symptoms were typically at least somewhat bothersome and sometimes exhibited a waxing-and-waning course. Some participants experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with performance of usual activities. The median visual analogue scale rating of general health was lower at 4 and 8 months compared with pre-COVID-19. Two clusters of symptom domains were identified. Conclusions: Many participants report bothersome symptoms following onset of COVID-19 with variable patterns of persistence and impact on quality of life. The substantial variability suggests the existence of multiple subphenotypes of PASC. A rigorous approach to the prospective measurement of symptoms and functional manifestations sets the stage for the next phase of research focusing on the pathophysiologic causes of the various subgroups of PASC.

7.
Open forum infectious diseases ; 2021.
Article in English | EuropePMC | ID: covidwho-1624185

ABSTRACT

BACKGROUND There is mounting evidence for the presence of post-acute sequelae of SARS-CoV-2 infection (PASC), but there is limited information on the spectrum, magnitude, duration, and patterns of these sequelae as well as their influence on quality of life. METHODS We assembled a cohort of adults with documented history of SARS-CoV-2 RNA-positivity who were ≥ 2 weeks past onset of COVID-19 symptoms or, if asymptomatic, first positive test. At 4-month intervals, we queried physical and mental health symptoms and quality of life. RESULTS Of the first 179 participants enrolled, 10 were asymptomatic during the acute phase of SARS-CoV-2 infection, 125 symptomatic but not hospitalized, and 44 symptomatic and hospitalized. During the post-acute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping and anosmia/dysgeusia were most common through 8 months of observation. Symptoms were typically at least somewhat bothersome and sometimes exhibited a waxing-and-waning course. Some participants experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with performance of usual activities. The median visual analogue scale rating of general health was lower at 4 and 8 months compared to pre-COVID-19. Two clusters of symptom domains were identified. CONCLUSION Many participants report bothersome symptoms following onset of COVID-19 with variable patterns of persistence and impact on quality of life. The substantial variability suggests the existence of multiple sub-phenotypes of PASC. A rigorous approach to the prospective measurement of symptoms and functional manifestations sets the stage for the next phase of research focusing on the pathophysiologic causes of the various sub-groups of PASC.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295855

ABSTRACT

Background As COVID-19 vaccines continue to be rolled-out, the “double burden” of health disparities in both exposure to infection and vaccination coverage intersect to determine the current and future patterns of infection, immunity, and mortality. Serology provides a unique opportunity to measure biomarkers of infection and vaccination simultaneously, and to relate these metrics to demographic and geographic factors. Methods Leveraging algorithmically selected residual serum samples from two hospital networks in San Francisco, we sampled 1014 individuals during February 2021, capturing transmission during the first 11 months of the epidemic and the early roll out of vaccination. These samples were tested using two serologic assays: one detecting antibodies elicited by infection, and not by vaccines, and one detecting antibodies elicited by both infection and vaccination. We used Bayesian statistical models to estimate the proportion of the population that was naturally infected and the proportion protected due to vaccination. Findings We estimated that the risk of prior infection of Latinx residents was 5.3 (95% CI: 3.2 - 10.3) times greater than the risk of white residents aged 18-64 and that white San Francisco residents over the age of 65 were twice as likely (2.0, 95% CI: 1.1 - 4.6) to be vaccinated as Black residents. We also found socioeconomically deprived zipcodes in the city had high probabilities of natural infections and lower vaccination coverage than wealthier zipcodes. Interpretation Using a platform we created for SARS-CoV-2 serologic data collection in San Francisco, we characterized and quantified the stark disparities in infection rates and vaccine coverage by demographic groups over the first year of the pandemic. While the arrival of the SARS-CoV-2 vaccine has created a ‘light at the end of the tunnel’ for this pandemic, ongoing challenges in achieving and maintaining equity must also be considered. Funding NIH, NIGMS, Schmidt Science Fellows in partnership with the Rhodes Trust and the Chan Zuckerberg Biohub.

9.
Arch Public Health ; 79(1): 125, 2021 Jul 07.
Article in English | MEDLINE | ID: covidwho-1496223

ABSTRACT

BACKGROUND: Early in the pandemic, inadequate SARS-CoV-2 testing limited understanding of transmission. Chief among barriers to large-scale testing was unknown feasibility, particularly in non-urban areas. Our objective was to report methods of high-volume, comprehensive SARS-CoV-2 testing, offering one model to augment disease surveillance in a rural community. METHODS: A community-university partnership created an operational site used to test most residents of Bolinas, California regardless of symptoms in 4 days (April 20th - April 23rd, 2020). Prior to testing, key preparatory elements included community mobilization, pre-registration, volunteer recruitment, and data management. On day of testing, participants were directed to a testing lane after site entry. An administrator viewed the lane-specific queue and pre-prepared test kits, linked to participants' records. Medical personnel performed sample collection, which included finger prick with blood collection to run laboratory-based antibody testing and respiratory specimen collection for polymerase chain reaction (PCR). RESULTS: Using this 4-lane model, 1,840 participants were tested in 4 days. A median of 57 participants (IQR 47-67) were tested hourly. The fewest participants were tested on day 1 (n = 338 participants), an intentionally lower volume day, increasing to n = 571 participants on day 4. The number of testing teams was also increased to two per lane to allow simultaneous testing of multiple participants on days 2-4. Consistent staffing on all days helped optimize proficiency, and strong community partnership was essential from planning through execution. CONCLUSIONS: High-volume ascertainment of SARS-CoV-2 prevalence by PCR and antibody testing was feasible when conducted in a community-led, drive-through model in a non-urban area.

10.
J Infect Dis ; 224(11): 1839-1848, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1483458

ABSTRACT

BACKGROUND: The biological processes associated with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are unknown. METHODS: We measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (<90 days) and late (>90 days) timepoints. We defined PASC as the presence of 1 or more coronavirus disease 2019 (COVID-19)-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed-effects models with terms for PASC and early and late recovery time periods. RESULTS: During early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including tumor necrosis factor-α (1.14-fold higher mean ratio [95% confidence interval {CI}, 1.01-1.28]; P = .028) and interferon-γ-induced protein 10 (1.28-fold higher mean ratio [95% CI, 1.01-1.62]; P = .038). Among those with PASC, there was a trend toward higher interleukin 6 levels during early recovery (1.29-fold higher mean ratio [95% CI, .98-1.70]; P = .07), which became more pronounced in late recovery (1.44-fold higher mean ratio [95% CI, 1.11-1.86]; P < .001). These differences were more pronounced among those with a greater number of PASC symptoms. CONCLUSIONS: Persistent immune activation may be associated with ongoing symptoms following COVID-19. Further characterization of these processes might identify therapeutic targets for those experiencing PASC.


Subject(s)
COVID-19 , Inflammation , Biomarkers/blood , COVID-19/complications , COVID-19/immunology , Cytokines/blood , Disease Progression , Humans , Inflammation/blood , Inflammation/virology
11.
Clin Infect Dis ; 73(Suppl 2): S127-S135, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1387758

ABSTRACT

BACKGROUND: There is an urgent need to understand the dynamics and risk factors driving ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during shelter-in-place mandates. METHODS: We offered SARS-CoV-2 reverse-transcription polymerase chain reaction (PCR) and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (aged ≥4 years) and workers in a San Francisco census tract (population: 5174) at outdoor, community-mobilized events over 4 days. We estimated SARS-CoV-2 point prevalence (PCR positive) and cumulative incidence (antibody or PCR positive) in the census tract and evaluated risk factors for recent (PCR positive/antibody negative) vs prior infection (antibody positive/PCR negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. RESULTS: We tested 3953 persons (40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black). Overall, 2.1% (83/3871) tested PCR positive: 95% were Latinx and 52% were asymptomatic when tested; 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR positive. Among 2598 tract residents, estimated point prevalence of PCR positives was 2.3% (95% confidence interval [CI], 1.2%-3.8%): 3.9% (95% CI, 2.0%-6.4%) among Latinx persons vs 0.2% (95% CI, .0-.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95% CI, 4.0%-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter in place and maintain income, frontline service work, unemployment, and household income <$50 000/year. Five SARS-CoV-2 phylogenetic lineages were detected. CONCLUSIONS: SARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Francisco's shelter-in-place ordinance.


Subject(s)
COVID-19 , SARS-CoV-2 , Emergency Shelter , Humans , Phylogeny , San Francisco/epidemiology
12.
Res Sq ; 2021 Feb 04.
Article in English | MEDLINE | ID: covidwho-1389923

ABSTRACT

Serosurveillance provides a unique opportunity to quantify the proportion of the population that has been exposed to pathogens. Here, we developed and piloted Serosurveillance for Continuous, ActionabLe Epidemiologic Intelligence of Transmission (SCALE-IT), a platform through which we systematically tested remnant samples from routine blood draws in two major hospital networks in San Francisco for SARS-CoV-2 antibodies during the early months of the pandemic. Importantly, SCALE-IT allows for algorithmic sample selection and rich data on covariates by leveraging electronic medical record data. We estimated overall seroprevalence at 4.2%, corresponding to a case ascertainment rate of only 4.9%, and identified important heterogeneities by neighborhood, homelessness status, and race/ethnicity. Neighborhood seroprevalence estimates from SCALE-IT were comparable to local community-based surveys, while providing results encompassing the entire city that have been previously unavailable. Leveraging this hybrid serosurveillance approach has strong potential for application beyond this local context and for diseases other than SARS-CoV-2.

13.
Sci Transl Med ; 13(612): eabh2624, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1371845

ABSTRACT

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN­specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non­COVID-19 controls revealed a lack of type I IFN­stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN­specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN­specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.


Subject(s)
Autoantibodies , COVID-19 , Interferon Type I , Autoantibodies/immunology , COVID-19/immunology , Humans , Interferon Type I/immunology
14.
Cell Rep ; 36(6): 109518, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1345269

ABSTRACT

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses.


Subject(s)
COVID-19/complications , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/pathology , Disease Progression , Female , Humans , Male , Middle Aged , Severity of Illness Index , Virus Shedding/immunology
15.
Sci Adv ; 7(31)2021 Jul.
Article in English | MEDLINE | ID: covidwho-1334521

ABSTRACT

Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

16.
BMC Med ; 19(1): 116, 2021 05 07.
Article in English | MEDLINE | ID: covidwho-1219073

ABSTRACT

BACKGROUND: COVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks. METHODS: We developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase chain reaction (PCR) surveys conducted during COVID-19 outbreaks in five homeless shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing, and universal mask wearing. RESULTS: The proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6 to 51.6%, which translated to the basic reproduction number (R0) estimates of 2.9-6.2. With moderate community incidence (~ 30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk (R0 = 1.5), moderate-risk (R0 = 2.9), and high-risk (R0 = 6.2) shelter were respectively 0.35, 0.13, and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27, and 0.08 for universal masking; and 0.74, 0.42, and 0.19 for these strategies in combination. The probability of averting an outbreak diminished with higher transmissibility (R0) within the simulated shelter and increasing incidence in the local community. CONCLUSIONS: In high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom screening, frequent PCR testing, and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/prevention & control , Computer Simulation , Disease Outbreaks/prevention & control , Homeless Persons , Infection Control/methods , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing/statistics & numerical data , Cities/epidemiology , Cities/statistics & numerical data , Computer Simulation/statistics & numerical data , Cross-Sectional Studies , Disease Outbreaks/statistics & numerical data , Homeless Persons/statistics & numerical data , Housing/statistics & numerical data , Humans , Infection Control/statistics & numerical data , Mass Screening/methods , Mass Screening/statistics & numerical data , United States/epidemiology
17.
Nat Biotechnol ; 39(8): 928-935, 2021 08.
Article in English | MEDLINE | ID: covidwho-1152862

ABSTRACT

Current serology tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies mainly take the form of enzyme-linked immunosorbent assays, chemiluminescent microparticle immunoassays or lateral flow assays, which are either laborious, expensive or lacking sufficient sensitivity and scalability. Here we present the development and validation of a rapid, low-cost, solution-based assay to detect antibodies in serum, plasma, whole blood and to a lesser extent saliva, using rationally designed split luciferase antibody biosensors. This new assay, which generates quantitative results in 30 min, substantially reduces the complexity and improves the scalability of coronavirus disease 2019 (COVID-19) antibody tests. This assay is well-suited for point-of-care, broad population testing, and applications in low-resource settings, for monitoring host humoral responses to vaccination or viral infection.


Subject(s)
Antibodies, Viral/blood , Biosensing Techniques/methods , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Point-of-Care Systems , SARS-CoV-2/immunology , COVID-19/virology , Humans , Luminescence
18.
Lancet Infect Dis ; 21(7): 929-938, 2021 07.
Article in English | MEDLINE | ID: covidwho-1145005

ABSTRACT

BACKGROUND: Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown. METHODS: In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection). FINDINGS: We estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144-12831) infectious days with 649 (505-950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917-8677), a reduction of 36% (29-41) compared with the base case, and identified 569 (88% [76-92]) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2520 days (1849-4158), a reduction of 70% (64-75) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126-9081), a reduction of 32% (26-38) compared with the base case, and identified 560 (86% [83-89]) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 3124 (2356-495), a reduction of 63% (58-66) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714-7679), a reduction of 42% (35-49) compared with the base case. INTERPRETATION: Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting. FUNDING: University of California, San Francisco.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Carrier State/diagnosis , Pandemics/prevention & control , Aircraft/statistics & numerical data , Asymptomatic Infections , COVID-19/transmission , COVID-19/virology , Carrier State/virology , Computer Simulation , Diagnostic Tests, Routine/statistics & numerical data , Humans , SARS-CoV-2/pathogenicity , Travel/statistics & numerical data
19.
Cells ; 10(2)2021 02 13.
Article in English | MEDLINE | ID: covidwho-1085116

ABSTRACT

As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, n = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects.


Subject(s)
COVID-19/complications , Extracellular Vesicles/pathology , Nervous System Diseases/etiology , Adult , Aged , Amyloid beta-Peptides/analysis , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , COVID-19/pathology , Female , Humans , Immunoglobulin G/blood , Interleukin-4/blood , Interleukin-6/blood , Male , Middle Aged , Nervous System Diseases/blood , Nervous System Diseases/pathology , Neurofilament Proteins/analysis , Neurogranin/analysis , Neurons/pathology , tau Proteins/analysis
20.
Open Forum Infect Dis ; 8(1): ofaa531, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1069285

ABSTRACT

BACKGROUND: Limited systematic surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the early months of the US epidemic curtailed accurate appraisal of transmission intensity. Our objective was to perform case detection of an entire rural community to quantify SARS-CoV-2 transmission using polymerase chain reaction (PCR) and antibody testing. METHODS: We conducted a cross-sectional survey of SARS-CoV-2 infection in the rural town of Bolinas, California (population 1620), 4 weeks after shelter-in-place orders. Participants were tested between April 20 and 24, 2020. Prevalence by PCR and seroprevalence from 2 forms of antibody testing were performed in parallel (Abbott ARCHITECT immunoglobulin [Ig]G and in-house IgG enzyme-linked immunosorbent assay). RESULTS: Of 1891 participants, 1312 were confirmed Bolinas residents (>80% community ascertainment). Zero participants were PCR positive. Assuming 80% sensitivity, it would have been unlikely to observe these results (P < .05) if there were >3 active infections in the community. Based on antibody results, estimated prevalence of prior infection was 0.16% (95% credible interval [CrI], 0.02%-0.46%). The positive predictive value (PPV) of a positive result on both tests was 99.11% (95% CrI, 95.75%-99.94%), compared with PPV 44.19%-63.32% (95% CrI, 3.25%-98.64%) if 1 test was utilized. CONCLUSIONS: Four weeks after shelter-in-place, SARS-CoV-2 infection in a rural Northern California community was extremely rare. In this low-prevalence setting, use of 2 antibody tests increased seroprevalence estimate precision. This was one of the first community-wide studies to successfully implement synchronous PCR and antibody testing, particularly in a rural setting. Widespread testing remains an underpinning of effective disease control in conjunction with consistent uptake of public health measures.

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