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1.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-337540

ABSTRACT

Background: The benefit of vaccination in people who experienced a prior SARS-CoV-2 infection remains unclear. Objective: To estimate the effectiveness of primary (two-dose) and booster (third dose) vaccination against Omicron infection among people with a prior documented infection. Design: Test-negative case-control study. Setting: Yale New Haven Health System facilities. Participants: Vaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022. Measurements: We conducted two analyses, each with an outcome of Omicron BA.1 infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary and booster vaccination. 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 (6.1% and 7.8% occurred following a prior infection, respectively). The effectiveness of primary vaccination 14-149 days after 2nd dose was 36.1% (CI, 7.1% to 56.1%) for people with and 28.5% (CI, 20.0% to 36.2%) without prior infection. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (CI, 0.56 to 1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (CI, 0.46 to 0.56). Limitations: Misclassification, residual confounding, reliance on TaqPath assay analyzed samples. Conclusion: While primary vaccination provided protection against BA.1 infection among people with and without prior infection, booster vaccination was only associated with additional protection in people without 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.

2.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816919

ABSTRACT

Cancer patients display immunomodulation related to malignancy and anti-cancer therapies, but how these factors impact COVID-19 remains unknown. To investigate immune responses in cancer patients with COVID-19, we undertook a prospective case-control study, enrolling hospitalized solid tumor patients with acute COVID-19, as well as age-, gender-, and comorbidity-matched COVID-19 patients without cancer as controls. Using biospecimens collected during hospitalization, we performed virologic measurements as well as in-depth immunophenotyping of cellular, antibody and cytokine responses. We enrolled 17 cancer patients (cases) admitted to Yale-New Haven Hospital between March 15 and June 30, 2020 with COVID-19, as well as 17 matched non-cancer patients (controls) admitted with COVID-19. No significant differences were observed between cases and controls based on patient characteristics (age, gender, race, co-morbidities, smoking history, days from symptom onset to COVID-19 diagnosis) or outcomes (COVID-19 severity, length of hospital stay, rate of intubation or mortality). The most common primary tumor sites were lung (4/17) and gastrointestinal (4/17);all cases had received cancer-directed therapy within 6 months of COVID-19 diagnosis, with 13/17 receiving treatment less than 1 month prior to hospitalization. Three of 17 cases had received immune checkpoint inhibitor therapies. Despite having similar SARS-CoV-2 viral RNA loads at the time of COVID-19 diagnosis when compared with controls, cancer cases had increased viral RNA abundance during hospitalization, suggesting slower clearance. Antibody responses against SARS-CoV-2 were preserved in cancer cases, with cases displaying similar levels of IgM and IgG antibodies directed against SARS-CoV-2 epitopes compared to controls. Cytokine profiling revealed higher plasma levels of CCL3, IL1A and CXCL12 in cancer cases compared to controls. Using flow cytometric immunophenotyping, we found that innate immune and non-T cell adaptive immune parameters were similar between cases and controls hospitalized with COVID-19. However, among cancer cases on conventional therapies, T cell lymphopenia was more profound, and these cases demonstrated higher levels of CD8+ exhausted (CD8+CD45RA-PD1+TIM3+ ), CD8+GranzymeB+ and CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ activated T cells when compared with controls;interestingly, these differences were not observed in patients who had received immune checkpoint inhibition. Thus, we found reduced viral RNA clearance and specific alterations in T cell and cytokine responses in cancer patients hospitalized with COVID-19 compared with matched controls with COVID-19. This dysregulated T cell response in cancer patients, which may reflect immune modulation due to chronic antigen stimulation as well as cancer therapies, may lead to altered virologic and clinical outcomes in this population.

3.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-334270

ABSTRACT

BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. CONCLUSION: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

4.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333683

ABSTRACT

Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro . Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset (~13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.

5.
Open Forum Infectious Diseases ; 8(SUPPL 1):S257, 2021.
Article in English | EMBASE | ID: covidwho-1746692

ABSTRACT

Background. Streptococcus pneumoniae (pneumococcus) is a common colonizer of the upper respiratory tract and can progress to cause invasive and mucosal disease. Additionally, infection with pneumococcus can complicate respiratory viral infections (influenza, respiratory syncytial virus, etc.) by exacerbating the initial disease. Limited data exist describing the potential relationship of SARS-CoV-2 infection with pneumococcus and the role of co-infection in influencing COVID-19 severity. Methods. Inpatients and healthcare workers testing positive for SARS-CoV-2 during March-August 2020 were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and for inpatients only, serotype-specific urine antigen detection (UAD) assays (to identify pneumococcal pneumonia). A multinomial multivariate regression model was used to examine the relationship between pneumococcal detection and COVID-19 severity. Results. Among the 126 subjects who tested positive for SARS-CoV-2, the median age was 62 years;54.9% of subjects were male;88.89% were inpatients;23.5% had an ICU stay;and 13.5% died. Pneumococcus was detected in 17 subjects (13.5%) by any method, including 5 subjects (4.0%) by RT-qPCR and 12 subjects (13.6%) by UAD. Little to no bacterial growth was observed on 21/235 culture plates. Detection by UAD was associated with both moderate and severe COVID-19 disease while RT-qPCR detection in saliva was not associated with severity. None of the 12 individuals who were UAD-positive died. Conclusion. Pneumococcal pneumonia (as determined by UAD) continues to occur during the ongoing pandemic and may be associated with more serious COVID-19 outcomes. Detection of pneumococcal carriage may be masked by high levels of antibiotic use. Future studies should better characterize the relationship between pneumococcus and SARS-CoV-2 across all disease severity levels.

6.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-330195

ABSTRACT

Objective: Real-world data have been critical for rapid-knowledge generation throughout the COVID-19 pandemic. To ensure high-quality results are delivered to guide clinical decision making and the public health response, as well as characterize the response to interventions, it is essential to establish the accuracy of COVID-19 case definitions derived from administrative data to identify infections and hospitalizations. Methods: Electronic Health Record (EHR) data were obtained from the clinical data warehouse of the Yale New Haven Health System (Yale, primary site) and 3 hospital systems of the Mayo Clinic (validation site). Detailed characteristics on demographics, diagnoses, and laboratory results were obtained for all patients with either a positive SARS-CoV-2 PCR or antigen test or ICD-10 diagnosis of COVID-19 (U07.1) between April 1, 2020 and March 1, 2021. Various computable phenotype definitions were evaluated for their accuracy to identify SARS-CoV-2 infection and COVID-19 hospitalizations. Results: Of the 69,423 individuals with either a diagnosis code or a laboratory diagnosis of a SARS-CoV-2 infection at Yale, 61,023 had a principal or a secondary diagnosis code for COVID-19 and 50,355 had a positive SARS-CoV-2 test. Among those with a positive laboratory test, 38,506 (76.5%) and 3449 (6.8%) had a principal and secondary diagnosis code of COVID-19, respectively, while 8400 (16.7%) had no COVID-19 diagnosis. Moreover, of the 61,023 patients with a COVID-19 diagnosis code, 19,068 (31.2%) did not have a positive laboratory test for SARS-CoV-2 in the EHR. Of the 20 cases randomly sampled from this latter group for manual review, all had a COVID-19 diagnosis code related to asymptomatic testing with negative subsequent test results. The positive predictive value (precision) and sensitivity (recall) of a COVID-19 diagnosis in the medical record for a documented positive SARS-CoV-2 test were 68.8% and 83.3%, respectively. Among 5,109 patients who were hospitalized with a principal diagnosis of COVID-19, 4843 (94.8%) had a positive SARS-CoV-2 test within the 2 weeks preceding hospital admission or during hospitalization. In addition, 789 hospitalizations had a secondary diagnosis of COVID-19, of which 446 (56.5%) had a principal diagnosis consistent with severe clinical manifestation of COVID-19 (e.g., sepsis or respiratory failure). Compared with the cohort that had a principal diagnosis of COVID-19, those with a secondary diagnosis had a more than 2-fold higher in-hospital mortality rate (13.2% vs 28.0%, P<0.001). In the validation sample at Mayo Clinic, diagnosis codes more consistently identified SARS-CoV-2 infection (precision of 95%) but had lower recall (63.5%) with substantial variation across the 3 Mayo Clinic sites. Similar to Yale, diagnosis codes consistently identified COVID-19 hospitalizations at Mayo, with hospitalizations defined by secondary diagnosis code with 2-fold higher in-hospital mortality compared to those with a primary diagnosis of COVID-19. Conclusions: COVID-19 diagnosis codes misclassified the SARS-CoV-2 infection status of many people, with implications for clinical research and epidemiological surveillance. Moreover, the codes had different performance across two academic health systems and identified groups with different risks of mortality. Real-world data from the EHR can be used to in conjunction with diagnosis codes to improve the identification of people infected with SARS-CoV-2.

7.
MEDLINE; 2022.
Preprint in English | MEDLINE | ID: ppcovidwho-329696

ABSTRACT

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate in a mouse model that SARS-CoV-2 infection can induce gut microbiome dysbiosis, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Comparison with stool samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

8.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-329416

ABSTRACT

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high transmissibility and recently swept the globe. Due to the extensive number of mutations, this variant has high level of immune evasion, which drastically reduced the efficacy of existing antibodies and vaccines. Thus, it is important to test an Omicron-specific vaccine, evaluate its immune response against Omicron and other variants, and compare its immunogenicity as boosters with existing vaccine designed against the reference wildtype virus (WT). Here, we generated an Omicron-specific lipid nanoparticle (LNP) mRNA vaccine candidate, and tested its activity in animals, both alone and as a heterologous booster to existing WT mRNA vaccine. Our Omicron-specific LNP-mRNA vaccine elicited strong and specific antibody response in vaccination-naive mice. Mice that received two-dose WT LNP-mRNA, the one mimicking the commonly used Pfizer/Moderna mRNA vaccine, showed a >40-fold reduction in neutralization potency against Omicron variant than that against WT two weeks post second dose, which further reduced to background level >3 months post second dose. As a booster shot for two-dose WT mRNA vaccinated mice, a single dose of either a homologous booster with WT LNP-mRNA or a heterologous booster with Omicron LNP-mRNA restored the waning antibody response against Omicron, with over 40-fold increase at two weeks post injection as compared to right before booster. Interestingly, the heterologous Omicron LNP-mRNA booster elicited neutralizing titers 10-20 fold higher than the homologous WT booster against the Omicron variant, with comparable titers against the Delta variant. All three types of vaccination, including Omicron mRNA alone, WT mRNA homologous booster, and Omicron heterologous booster, elicited broad binding antibody responses against SARS-CoV-2 WA-1, Beta, and Delta variants, as well as other Betacoronavirus species such as SARS-CoV, but not Middle East respiratory syndrome coronavirus (MERS-CoV). These data provided direct proof-of-concept assessments of an Omicron-specific mRNA vaccination in vivo, both alone and as a heterologous booster to the existing widely-used WT mRNA vaccine form.

9.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326947

ABSTRACT

Background. COVID-19 vaccines have proven highly effective among SARS-CoV-2 naive individuals, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with prior infection is less clear. Methods. Utilizing national COVID-19 notification, hospitalization, and vaccination datasets from Brazil, we performed a case-control study using a test-negative design to assess the effectiveness of four vaccines (CoronaVac, ChAdOx1, Ad26.COV2.S and BNT162b2) among individuals with laboratory-confirmed prior SARS-CoV-2 infection. We matched RT-PCR positive, symptomatic COVID-19 cases with RT-PCR-negative controls presenting with symptomatic illnesses, restricting both groups to tests performed 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 hospitalization or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. Findings. Among individuals with prior SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection ≥ 14 days from vaccine series completion was 39.4% (95% CI 36.1-42.6) for CoronaVac, 56.0% (95% CI 51.4-60.2) for ChAdOx1, 44.0% (95% CI 31.5-54.2) for Ad26.COV2.S, and 64.8% (95% CI 54.9-72.4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose compared with the first dose. Effectiveness against hospitalization or death ≥ 14 days from vaccine series completion was 81.3% (95% CI 75.3-85.8) for CoronaVac, 89.9% (95% CI 83.5-93.8) for ChAdOx1, 57.7% (95% CI -2.6-82.5) for Ad26.COV2.S, and 89.7% (95% CI 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. Provision of a full vaccine series to individuals following recovery from COVID-19 may 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 S.A., Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Generalitat de Catalunya.

10.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326635

ABSTRACT

Prior to the emergence of antigenically distinct SARS-CoV-2 variants, reinfections were reported infrequently - presumably due to the generation of durable and protective immune responses. However, case reports also suggested that rare, repeated infections may occur as soon as 48 days following initial disease onset. The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection - confirmed by whole virus genome sequencing - 7 months after primary infection. To elucidate the immunological mechanisms responsible for SARS-CoV-2 reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses. The patient's immune system was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we also identified the development of neutralizing antibodies and the formation of humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation in this patient. In summary, our study suggests that a low neutralizing antibody presence alone is not sufficient to confer resistance against reinfection. Thus, patients with solid organ transplantation, or patients who are otherwise immunosuppressed, who recover from infection with SARS-CoV-2 may not develop sufficient protective immunity and are at risk of reinfection.

11.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326567

ABSTRACT

Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.

12.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296673

ABSTRACT

SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but have not been reported in patients receiving treatment with the antiviral agent. We present a case of an immunocompromised patient with acquired B-cell deficiency who developed an indolent, protracted course of SARS-CoV-2 infection. Remdesivir therapy alleviated symptoms and produced a transient virologic response, but her course was complicated by recrudescence of high-grade viral shedding. Whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase, which was not present in pre-treatment specimens. In vitro experiments demonstrated that the mutation conferred a ~6-fold increase in remdesivir IC50 but resulted in a fitness cost in the absence of remdesivir. Sustained clinical and virologic response was achieved after treatment with casirivimab-imdevimab. Although the fitness cost observed in vitro may limit the risk posed by E802D, this case illustrates the importance of monitoring for remdesivir resistance and the potential benefit of combinatorial therapies in immunocompromised patients with SARS-CoV-2 infection.

14.
MEDLINE; 2020.
Preprint in English | MEDLINE | ID: ppcovidwho-290693

ABSTRACT

Background: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. Case presentation: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. Conclusion: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

15.
Open Forum Infectious Diseases ; 7(SUPPL 1):S313, 2020.
Article in English | EMBASE | ID: covidwho-1185854

ABSTRACT

Background: Data early in the SARS-CoV-2 pandemic suggested frontline healthcare workers (HCW) may account for 10-20% of all infections. CDC estimated 600,000 infections in HCWs. Symptom screening is a strategy to prevent healthcare-associated transmission. This method may not identify asymptomatic or pre-symptomatic carriers. Methods: We conducted a prospective cohort study in asymptomatic or minimally symptomatic healthcare workers in a 1541-bed academic medical center. Although recruitment began in designated COVID-19 units, we expanded to all HCWs providing care to hospitalized patients during the pandemic. Data was gathered on demographics, work area in the hospital and daily questionnaires were sent listing symptoms of SARS-CoV-2. Protocol included twice weekly self-collected nasopharyngeal swab and saliva for SARS-CoV-2 N1 and N2.Those with positive PCR result, underwent telephone survey to assess symptomatology and severity of illness. Results: A total 525 HCWs began the study protocol and 16 were identified as PCR positive. Samples included concordant saliva and NP samples on 9 (56%), exclusively NP samples on 5 (31%) and 2 (12%) HCWs were positive by saliva PCR only. Majority were female, and all were nursing staff;with 19% reported not working in a designated COVID-19 unit. During the course of this active surveillance, universal masking was mandated in the institution. Rhinorrhea and headache were reported by 6 (38%), 5 (31%) reported cough and 3 (19%) developed myalgia. Changes in smell and taste preceded the positive PCR test in 2 (12%). One HCW reported developing a fever with acute illness. All were notified about their PCR positive status by institution's occupational health department and self-isolated to monitor for symptoms. Conclusion: The spectrum of disease in this HCW cohort is similar to mild disease in the community. Due to high incidence of asymptomatic or mildly symptomatic HCWs, active surveillance with routine testing proves be beneficial to prevent hospital transmission of SARS-CoV-2. Universal masking significantly decreased the HCW positive rate in our study, underscoring the need for universal efforts to mitigate healthcare-associated transmission with self-monitoring, face mask use, and other infection prevention behaviors like hand hygiene.

16.
Open Forum Infectious Diseases ; 7(SUPPL 1):S295-S296, 2020.
Article in English | EMBASE | ID: covidwho-1185818

ABSTRACT

Background: Smell loss has been recognized as an important, and potentially early, sign of COVID-19. However, to date smell loss has only been assessed in retrospective, COVID+ cohorts, and largely through self-report. The objective of this study was to implement a daily standardized behavioral test of smell sensitivity in healthcare workers (HCW) to capture changes in smell sensitivity over time and to assess whether these changes occur prior to positive COVID test. Methods: The study enrolled 500 high-risk COVID-negative HCW during the COVID-19 epidemic in Connecticut, beginning March 28, 2020 (80% F, mean age 38, 58% nurses). Initially, HCW received a daily symptom questionnaire with parosmia screening questions. On April 23 we introduced the “Jiffy”, a daily at-home psychophysical test of smell sensitivity, where olfactory stimuli are sampled and rated for perceived intensity. SARS-CoV-2 infection was tested every three days by PCR of nasopharyngeal swabs or saliva Results: Of the first 500 enrolled HCW, 376 HCW (75%) completed the Jiffy 4528 times (mean 12 times/HCW). 17/500 HCW (3.4%) had a COVID+ test, of which 9/17 (53%) reported smell loss through the Jiffy or the daily symptom survey. 6/9 (67%) reported smell loss that preceded or was concurrent with a COVID+ test. 8/17 COVID+ HCW completed the Jiffy, with 5/8 (63%) reporting reductions in smell versus 42/368 (11%) COVID- HCW (OR=13, 95% CI: 2.4-85, p=.001). COVID+ HCW rated their greatest reduction in smell sensitivity as slight (40%) and severe (60%), versus slight (88%) and moderate (12%) in COVID- HCW. 16/17 COVID+ HCW completed a daily symptom survey (mean 14 times/HCW), with 8/16 (50%) ever reporting parosmia versus 90/466 (19%) of COVID- HCW (OR=4.2, 95% CI: 1.3-13, p=.007). Overall, parosmia was the first reported symptom in 3/13 (23%) COVID+ HCW who reported symptoms. Conclusion: We conducted a prospective study of smell testing in a population at high risk for COVID-19 using two parallel approaches. Our results demonstrate the feasibility of at-home smell testing for assessing parosmia during COVID-19, in some cases even prior to a positive PCR result. Given the urgent need for widespread, lowcost, non-invasive testing for COVID-19, we are now developing an easy-to-use app to distribute this survey more widely to high-risk populations. (Table Presented).

17.
Open Forum Infectious Diseases ; 7(SUPPL 1):S165, 2020.
Article in English | EMBASE | ID: covidwho-1185700

ABSTRACT

Background: Initial CDC recommendations for passive monitoring of COVID-19 related symptoms among staff may not be sufficient in preventing the introduction and transmission of SARS-CoV-2 in healthcare settings. We therefore implemented active monitoring for SARS-CoV-2 infection in healthcare workers (HCWs) at an academic medical center during the COVID-19 epidemic in northeast US. Methods: We recruited a cohort of HCWs at Yale New Haven Hospital who worked in COVID-19 units and did not have COVID-19 related symptoms between March 28 and June 1, 2020. During follow-up, participants provided daily information on symptoms by responding to a web-based questionnaire, self-administered nasopharyngeal (NP) and saliva specimens every 3 days, and blood specimens every 14 days. We performed SARS-CoV-2 RT-PCR and an anti-spike protein IgM and IgG ELISA to identify virological and serological-confirmed infection, respectively. Results: We enrolled 525 (13%) amongst 4,136 HCW of whom daily information on symptoms and NP, saliva, and blood specimens were obtained for 66% (of 13208), 42% (or 1977), 44% (of 2071) and 65% (of 1099), respectively, of the follow-up measurement points. We identified 16 (3.0% of 525) HCWs with PCR-confirmed SARS-CoV-2 infection and an additional 12 (2.3% of 525) who were not tested by PCR or had negative PCR results but had serological evidence of infection. The overall cumulative incidence of SARS-CoV-2 infection was 5.3% (28 of 525) amongst HCWs. Cases were not identified by hospital protocols for passive staff self-monitoring for symptoms. Amongst 16 PCR-confirmed cases, 9 (56%) of the 16 PCR-confirmed HCW had symptoms during or after the date of initial detection. We did not identify an epidemiological link between the 28 confirmed cases. Conclusion: We found that a significant proportion (5.3%) of HCWs were infected with SARS-CoV-2 during the COVID-19 epidemic. In the setting of universal PPE use, infections were possibly acquired in the community rather than stemming from patient-HCW or HCW-HCW transmission. Passive monitoring of symptoms is inadequate in preventing introductions of SARS-CoV-2 into the healthcare setting due to asymptomatic and oligosymptomatic presentations.

18.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-3028

ABSTRACT

The COVID-19 pandemic has affected more than 10 million people worldwide with mortality exceeding half a million patients. Risk factors associated with severe disease and mortality include advanced age, hypertension, diabetes, and obesity.<sup>1</sup> Clear mechanistic understanding of how these comorbidities converge to enable severe infection is lacking. Notably each of these risk factors pathologically disrupts the lipidome and this disruption may be a unifying feature of severe COVID-19.<sup>1-7</sup> Here we provide the first in depth interrogation of lipidomic changes, including structural-lipids as well as the eicosanoids and docosanoids lipid mediators (LMs), that mark COVID-19 disease severity. Our data reveal that progression from moderate to severe disease is marked by a loss of specific immune regulatory LMs and increased pro-inflammatory species. Given the important immune regulatory role of LMs, these data provide mechanistic insight into the immune balance in COVID-19 and potential targets for therapy with currently approved pharmaceuticals.<sup>8</sup>.

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