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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337685

ABSTRACT

ABSTRACT B ackground Prisons and jails are high-risk settings for Covid-19 transmission, morbidity, and mortality. We evaluate protection conferred by prior infection and vaccination against the SARS-CoV-2 Omicron variant within the California state prison system. M ethods We employed a test-negative design to match resident and staff cases during the Omicron wave (December 24, 2021—April 14, 2022) to controls according to a case’s test-week as well as demographic, clinical, and carceral characteristics. We estimated protection against infection using conditional logistic regression, with exposure status defined by vaccination, stratified by number of mRNA doses received, and prior infection, stratified by periods before or during Delta variant predominance. R esults We matched 15,783 resident and 8,539 staff cases to 180,169 resident and 90,409 staff controls. Among cases, 29.7% and 2.2% were infected before or during the emergence of the Delta variant, respectively;30.6% and 36.3% were vaccinated with two or three doses, respectively. Estimated protection from Omicron infection for two and three doses were 14.9% (95% Confidence Interval [CI], 12.3—19.7%) and 43.2% (42.2—47.4%) for those without known prior infections, 47.8% (95% CI, 46.6—52.8%) and 61.3% (95% CI, 60.7—64.8%) for those infected before the emergence of Delta, and 73.1% (95% CI, 69.8—80.1%) and 86.8% (95% CI, 82.1—92.7) for those infected during the period of Delta predominance. C onclusion A third mRNA dose provided significant, additional protection over two doses, including among individuals with prior infection. Our findings suggest that vaccination should remain a priority—even in settings with high levels of transmission and prior infection.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337679

ABSTRACT

Background The limited variation observed among SARS-CoV-2 consensus sequences makes it difficult to reconstruct transmission linkages in outbreak settings. Previous studies have recovered variation within individual SARS-CoV-2 infections but have not yet measured the informativeness of within-host variation for transmission inference. Methods We performed tiled amplicon sequencing on 307 SARS-CoV-2 samples from four prospective studies and combined sequence data with household membership data, a proxy for transmission linkage. Results Consensus sequences from households had limited diversity (mean pairwise distance, 3.06 SNPs;range, 0-40). Most (83.1%, 255/307) samples harbored at least one intrahost single nucleotide variant (iSNV;median: 117;IQR: 17-208), when applying a liberal minor allele frequency of 0.5% and prior to filtering. A mean of 15.4% of within-host iSNVs were recovered one day later. Pairs in the same household shared significantly more iSNVs (mean: 1.20 iSNVs;95% CI: 1.02-1.39) than did pairs in different households infected with the same viral clade (mean: 0.31 iSNVs;95% CI: 0.28-0.34), a signal that increases with increasingly liberal thresholds. Conclusions Although only a subset of within-host variation is consistently shared across likely transmission pairs, shared iSNVs may augment the information in consensus sequences for predicting transmission linkages.

3.
Cell Rep Med ; 3(6): 100640, 2022 Jun 21.
Article in English | MEDLINE | ID: covidwho-1852243

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4+ longitudinal dynamics following infection and of 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 interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγ-IL-21-TNF-α+ CD4+ T cells the predominant population detected at later time points. Greater percentages of IFNγ-IL-21-TNF-α+ CD4+ T cells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7 months post-infection (⍴ = 0.4, p = 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ- and TNF-α-producing, spike-protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , CD4-Positive T-Lymphocytes , Humans , Outpatients , T-Lymphocytes , Tumor Necrosis Factor-alpha
4.
Clin Infect Dis ; 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1806309

ABSTRACT

BACKGROUND: Favipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries. METHODS: We conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1: 1 to receive placebo or favipiravir (1800mg BID Day 1, 800 mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis. RESULTS: From July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48-1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54-1.29; sustained: HR 0.87, 95% CI 0.52-1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment. CONCLUSIONS: Our data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334227

ABSTRACT

Importance The benefit of primary and booster vaccination in people who experienced prior SARS-CoV-2 infection remains unclear. Objective To estimate the effectiveness of a primary (two-dose) and booster (third dose) vaccination against Omicron infection among previously infection people. Design Test-negative case-control study. Setting Yale New Haven Health System facilities serving southern Connecticut communities. Participants Vaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022. Exposure COVID-19 mRNA primary and booster vaccination. Main Outcomes and Measures We conducted two analyses, each with an outcome of Omicron BA.1 variant infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary vaccination during the period before and during booster eligibility (14-149 and ≥150 days, respectively, after 2 nd dose) and of booster vaccination (≥14 days after booster dose). To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people. Results Overall, 10,676 cases and 119,397 controls were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 6.1% and 7.8% had a prior infection. The effectiveness of primary vaccination 14-149 days after 2 nd dose was 36.1% (95% CI, 7.1-56.1%) and 28.5% (95% CI, 20.0-36.2%) for people with and without prior infection, respectively. The effectiveness of booster vaccination was 45.8% (95% CI, 20.0-63.2%) and 56.9% (95% CI, 52.1-61.2%) in people with and without prior infection, respectively. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (95% CI, 0.56-1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (95% CI, 0.46-0.56). Conclusions and Relevance Primary vaccination provided significant but limited protection against Omicron BA.1 infection among people with and without prior infection. While booster vaccination was associated with additional protection in people without prior infection, it was not associated with additional protection among people with prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.

6.
BMJ Open ; 12(4): e055206, 2022 04 15.
Article in English | MEDLINE | ID: covidwho-1794498

ABSTRACT

OBJECTIVES: To evaluate the risk of exposure to SARS-CoV-2 in naturally ventilated hospital settings by measuring parameters of ventilation and comparing these findings with results of bioaerosol sampling. STUDY DESIGN: Cross-sectional study. STUDY SETTING AND STUDY SAMPLE: The study sample included nine hospitals in Dhaka, Bangladesh. Ventilation characteristics and air samples were collected from 86 healthcare spaces during October 2020 to February 2021. PRIMARY OUTCOME: Risk of cumulative SARS-CoV-2 infection by type of healthcare area. SECONDARY OUTCOMES: Ventilation rates by healthcare space; risk of airborne detection of SARS-CoV-2 across healthcare spaces; impact of room characteristics on absolute ventilation; SARS-CoV-2 detection by naturally ventilated versus mechanically ventilated spaces. RESULTS: The majority (78.7%) of naturally ventilated patient care rooms had ventilation rates that fell short of the recommended ventilation rate of 60 L/s/p. Using a modified Wells-Riley equation and local COVID-19 case numbers, we found that over a 40-hour exposure period, outpatient departments posed the highest median risk for infection (7.7%). SARS-CoV-2 RNA was most frequently detected in air samples from non-COVID wards (50.0%) followed by outpatient departments (42.9%). Naturally ventilated spaces (22.6%) had higher rates of SARS-CoV-2 detection compared with mechanically ventilated spaces (8.3%), though the difference was not statistically significant (p=0.128). In multivariable linear regression with calculated elasticity, open door area and cross-ventilation were found to have a significant impact on ventilation. CONCLUSION: Our findings provide evidence that naturally ventilated healthcare settings may pose a high risk for exposure to SARS-CoV-2, particularly among non-COVID-designated spaces, but improving parameters of ventilation can mitigate this risk.


Subject(s)
COVID-19 , SARS-CoV-2 , Bangladesh/epidemiology , COVID-19/epidemiology , Cross-Sectional Studies , Delivery of Health Care , Humans , RNA, Viral , Ventilation
7.
Med (N Y) ; 3(6): 371-387.e9, 2022 Jun 10.
Article in English | MEDLINE | ID: covidwho-1783640

ABSTRACT

Background: COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.1 , SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.2, 3, 4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.5. Methods: We analyzed the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms. Findings: Fecal SARS-CoV-2 RNA is detected in 49.2% [95% confidence interval, 38.2%-60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4 months, 12.7% [8.5%-18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%-7.3%] shed at 7 months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA. Conclusions: The extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19. Funding: This research was supported by a Stanford ChemH-IMA grant; fellowships from the AACR and NSF; and NIH R01-AI148623, R01-AI143757, and UL1TR003142.


Subject(s)
COVID-19 , Communicable Diseases , Gastrointestinal Diseases , COVID-19/diagnosis , COVID-19 Testing , Feces , Gastrointestinal Diseases/diagnosis , Humans , Lung , RNA, Viral/genetics , SARS-CoV-2/genetics
8.
Epidemiology ; 33(4): 450-456, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1778957

ABSTRACT

Postauthorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. Although bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper, we introduce a theoretical framework to describe the interpretation of such a bias indicator in test-negative studies, and outline strong assumptions that would allow vaccine effectiveness among recently vaccinated individuals to serve as a negative control exposure.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Case-Control Studies , Humans , Vaccination
9.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332543

ABSTRACT

Summary Background Large outbreaks of the SARS-CoV-2 Omicron (B.1.1.529) variant have occurred in countries with high coverage of inactivated Covid-19 vaccines, raising urgent questions about effectiveness of these vaccines against disease and hospitalization with Omicron. Methods We conducted a nationwide, test-negative, case-control study of adults who were tested for SARS-CoV-2 infection. We evaluated vaccine effectiveness against symptomatic Covid-19 and severe Covid-19 (hospital admission or deaths) for the primary series of CoronaVac and homologous and heterologous (BNT162b2) booster doses. Findings Between September 6, 2021, and March 10, 2022, a total of 1,339,986 cases were matched to 1,339,986 test-negative controls. In the period of Omicron predominance, vaccine effectiveness ≥180 days after the second CoronaVac dose was 8·1% (95% CI, 7·0 to 9·1) and 57·0% (95% CI, 53·5 to 60·2) against symptomatic and severe Covid-19, respectively. Vaccine effectiveness against symptomatic disease was 15·0% (95% CI, 12·0 to 18·0) and 56·8% (95% CI, 56·3 to 57·4) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, vaccine effectiveness against severe Covid-19 was 71·3% (95% CI, 60·3 to 79·2) and 85·5% (95% CI, 83·3 to 87·0) after receiving a homologous and heterologous booster, respectively. Whereas waning of vaccine effectiveness against symptomatic Covid-19 was observed ≥90 days after a homologous and heterologous booster, waning against severe Covid-19 was only observed after a homologous booster. Interpretation A homologous CoronaVac booster dose provided limited additional protection, while a BNT162b2 booster dose afforded sustained protection against severe disease for at least three months.

10.
Clin Infect Dis ; 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1769227

ABSTRACT

BACKGROUND: An immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. METHODS: The performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. RESULTS: The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. CONCLUSIONS: The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.

11.
Lancet Infect Dis ; 22(6): 791-801, 2022 06.
Article in English | MEDLINE | ID: covidwho-1768665

ABSTRACT

BACKGROUND: COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. METHODS: Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. FINDINGS: Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1-42·6) for CoronaVac, 56·0% (51·4-60·2) for ChAdOx1 nCoV-19, 44·0% (31·5-54·2) for Ad26.COV2.S, and 64·8% (54·9-72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3-85·8) for CoronaVac, 89·9% (83·5-93·8) for ChAdOx1 nCoV-19, 57·7% (-2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3-97·7) for BNT162b2. INTERPRETATION: All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. FUNDING: Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.


Subject(s)
COVID-19 Vaccines , COVID-19 , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Case-Control Studies , Humans , SARS-CoV-2
13.
Prev Med Rep ; 27: 101771, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1740104

ABSTRACT

Carceral facilities are high-risk settings for COVID-19 transmission. Factors associated with COVID-19 vaccine acceptance and hesitancy among incarcerated individuals are poorly understood, especially among jail residents. Here, we conducted a retrospective review of electronic health record (EHR) data on COVID-19 vaccine uptake in custody and additionally administered a survey to assess reasons for vaccine hesitancy, sources of COVID-19 information, and medical mistrust among residents of four Northern California jails. We performed multivariate logistic regression to determine associations with vaccine acceptance. Of 2,564 jail residents offered a COVID-19 vaccine between March 19, 2021 and June 30, 2021, 1,441 (56.2%) accepted at least one dose. Among vaccinated residents, 497 (34.5%) had initially refused. Vaccine uptake was higher among older individuals, women, those with recent flu vaccination, and those living in shared housing. Among 509 survey respondents, leading reasons for vaccine hesitancy were concerns around side effects and suboptimal efficacy, with cost and the need for an annual booster being other hypothetical deterrents to vaccination. Vaccine hesitancy was also associated with mistrust of medical personnel in and out of jail, although this association varied by race/ethnicity. Television and friends/family were the most common and most trusted sources of COVID-19 information, respectively. Overall, vaccine acceptance was much lower among jail residents than the local and national general population. Interventions to increase vaccination rates in this setting should utilize accessible and trusted sources of information to address concerns about side effects and efficacy, while working to mitigate medical and institutional mistrust among residents.

14.
Clin Infect Dis ; 2022 Jan 27.
Article in English | MEDLINE | ID: covidwho-1713625

ABSTRACT

BACKGROUND: Prisons and jails are high-risk settings for COVID-19. Vaccines may substantially reduce these risks, but evidence is needed on COVID-19 vaccine effectiveness for incarcerated people, who are confined in large, risky congregate settings. METHODS: We conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates, adjusted for resident characteristics and infection rates across prisons. RESULTS: Among 60,707 cohort members, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable: 74% [95% CI, 62-82%] and 92% [95% CI, 74-98%] from 14 days after first and second doses, respectively. CONCLUSIONS: Consistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination, and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population.

15.
Open Forum Infect Dis ; 9(1): ofab600, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1700044

ABSTRACT

We developed a simple, noninvasive mask sampling method to quantify and sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from exhaled breath. We found substantial variation between individuals in SARS-CoV-2 copies exhaled over a 15-minute period, which moderately correlated with nasal swab viral load. Talking was associated with a median of 2 log10 greater exhaled viral copies. Exposure varies substantially between individuals but may be risk stratified by nasal swab viral load and whether the exposure involved conversation.

16.
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.

17.
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.

18.
Open forum infectious diseases ; 9(1), 2021.
Article in English | EuropePMC | ID: covidwho-1619398

ABSTRACT

We developed a simple, noninvasive mask sampling method to quantify and sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from exhaled breath. We found substantial variation between individuals in SARS-CoV-2 copies exhaled over a 15-minute period, which moderately correlated with nasal swab viral load. Talking was associated with a median of 2 log10 greater exhaled viral copies. Exposure varies substantially between individuals but may be risk stratified by nasal swab viral load and whether the exposure involved conversation.

20.
Open forum infectious diseases ; 8(Suppl 1):S302-S302, 2021.
Article in English | EuropePMC | ID: covidwho-1563805

ABSTRACT

Background In order to mitigate the spread of SARS-CoV-2 and the COVID-19 pandemic, public health officials have recommended self-isolation, self-quarantine of exposed household contacts (HHC), and mask use to limit viral spread within households and communities. While household transmission of SARS-CoV-2 is common, risk factors for HHC transmission are poorly understood. Methods In this prospective cohort study, we enrolled 37 households with at least one reverse transcription polymerase chain reaction-confirmed (RT-PCR) COVID-19 index case from March 2020 - March 2021, in order to calculate secondary attack rates (SAR) and define risk factors for secondary infections. Participants were tested daily for SARS-CoV-2 via RT-PCR, using self-collected lower nasal samples. Households were followed until all members tested negative for seven consecutive days. We collected demographics, medical conditions, relationship to index case, and socioeconomic indicators. Subgroup data analysis was conducted and stratified by positivity status. Results Of 99 enrolled participants, 37 were index cases and 62 were household contacts (HHC), of whom 25 HHC were infected (40.3%). Secondary attack rate (SAR) was highest among adults caring for a parent (n=4/4, 100%) and parents of index cases (5/10, 50%). Households whose income came from service work had greater risk of transmission compared to households whose primary income was technology (n=5/7;71.4% vs 3/8;37.5% respectively). Pediatric contacts were at lower risk of infection when compared to adult contacts (n=5/18, 27.8% vs n=20/44, 45.5% respectively). Conclusion This study suggests that household transmission represents a key source of community-based infection of SARS-CoV-2. Allocating resources for education/training regarding prevention among infected individuals and their close contacts will be critical for control of future outbreaks of SARS-CoV-2. Disclosures All Authors: No reported disclosures

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