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Article ; Online: Use of Whole-Genome Sequencing to Estimate the Contribution of Immune Evasion and Waning Immunity on Decreasing COVID-19 Vaccine Effectiveness.

Lind, Margaret L / Copin, Richard / McCarthy, Shane / Coppi, Andreas / Warner, Fred / Ferguson, David / Duckwall, Chelsea / Borg, Ryan / Muenker, M Catherine / Overton, John / Hamon, Sara / Zhou, Anbo / Cummings, Derek A T / Ko, Albert I / Hamilton, Jennifer D / Schulz, Wade L / Hitchings, Matt D T

The Journal of infectious diseases

2022 Volume 227, Issue 5, Page(s) 663–674

Abstract: Background: The impact variant-specific immune evasion and waning protection have on declining coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) remains unclear. Using whole-genome sequencing (WGS), we examined the contribution these ... ...

Abstract	Background: The impact variant-specific immune evasion and waning protection have on declining coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) remains unclear. Using whole-genome sequencing (WGS), we examined the contribution these factors had on the decline that followed the introduction of the Delta variant. Furthermore, we evaluated calendar-period-based classification as a WGS alternative. Methods: We conducted a test-negative case-control study among people tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 April and 24 August 2021. Variants were classified using WGS and calendar period. Results: We included 2029 cases (positive, sequenced samples) and 343 727 controls (negative tests). VE 14-89 days after second dose was significantly higher against Alpha (84.4%; 95% confidence interval [CI], 75.6%-90.0%) than Delta infection (68.9%; 95% CI, 58.0%-77.1%). The odds of Delta infection were significantly higher 90-149 than 14-89 days after second dose (P value = .003). Calendar-period-classified VE estimates approximated WGS-classified estimates; however, calendar-period-based classification was subject to misclassification (35% Alpha, 4% Delta). Conclusions: Both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While calendar-period-classified VE estimates mirrored WGS-classified estimates, our analysis highlights the need for WGS when variants are cocirculating and misclassification is likely.
MeSH term(s)	Humans ; COVID-19 ; COVID-19 Vaccines ; Case-Control Studies ; Immune Evasion ; SARS-CoV-2 ; Vaccine Efficacy ; Hepatitis D
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac453
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Article ; Online: No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination.

Lu-Culligan, Alice / Tabachnikova, Alexandra / Pérez-Then, Eddy / Tokuyama, Maria / Lee, Hannah J / Lucas, Carolina / Silva Monteiro, Valter / Miric, Marija / Brache, Vivian / Cochon, Leila / Muenker, M Catherine / Mohanty, Subhasis / Huang, Jiefang / Kang, Insoo / Dela Cruz, Charles / Farhadian, Shelli / Campbell, Melissa / Yildirim, Inci / Shaw, Albert C /

Ma, Shuangge / Vermund, Sten H / Ko, Albert I / Omer, Saad B / Iwasaki, Akiko

PLoS biology

2022 Volume 20, Issue 5, Page(s) e3001506

Abstract: The impact of Coronavirus Disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated 2 of the most widely propagated claims to determine (1) whether COVID-19 mRNA vaccination of mice ... ...

Abstract	The impact of Coronavirus Disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated 2 of the most widely propagated claims to determine (1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities; and (2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from these murine pregnancies vaccinated prior to the formation of the definitive placenta exhibit high circulating levels of anti-spike and anti-receptor-binding domain (anti-RBD) antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) consistent with maternal antibody status, indicating transplacental transfer in the later stages of pregnancy after early immunization. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.
MeSH term(s)	Animals ; Antibodies, Viral ; COVID-19/prevention & control ; Female ; Fetus ; Gene Products, env ; Humans ; Mice ; Placenta/metabolism ; Pregnancy ; Pregnancy Proteins ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Viral ; Gene Products, env ; Pregnancy Proteins ; RNA, Messenger ; syncytin
Language	English
Publishing date	2022-05-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001506
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Article ; Online: Use of whole genome sequencing to estimate the contribution of immune evasion and waning immunity to decreasing COVID-19 vaccine effectiveness during alpha and delta variant waves

Lind, Margaret L / Copin, Richard / McCarthy, Shane / Coppi, Andreas / Warner, Fred / Ferguson, David / Duckwall, Chelsea / Borg, Ryan / Muenker, M Catherine / Overton, John / Hamon, Sara / Zhou, Anbo / Cummings, Derek AT / Ko, Albert I. / Hamilton, Jennifer D / Schulz, Wade / Hitchings, Matt T.

medRxiv

Abstract: Background: The decline in COVID-19 mRNA vaccine effectiveness (VE) is well established, however the impact of variant-specific immune evasion and waning protection remains unclear. Here, we use whole-genome-sequencing (WGS) to tease apart the ... ...

Abstract	Background: The decline in COVID-19 mRNA vaccine effectiveness (VE) is well established, however the impact of variant-specific immune evasion and waning protection remains unclear. Here, we use whole-genome-sequencing (WGS) to tease apart the contribution of these factors on the decline observed following the introduction of the Delta variant. Further, we evaluate the utility of calendar-period-based variant classification as an alternative to WGS. Methods: We conducted a test-negative-case-control study among people who received SARS-CoV-2 RT-PCR testing in the Yale New Haven Health System between April 1 and August 24, 2021. Variant classification was performed using WGS and secondarily by calendar-period. We estimated VE as one minus the ratio comparing the odds of infection among vaccinated and unvaccinated people. Results: Overall, 2,029 cases (RT-PCR positive, sequenced samples) and 343,985 controls (negative RT-PCRs) were included. VE 14-89 days after 2nd dose was significantly higher against WGS-classified Alpha infection (84.4%, 95% confidence interval: 75.6-90.0%) than Delta infection (68.9%, CI: 58.0-77.1%, p-value: 0.013). The odds of WGS-classified Delta infection were significantly higher 90-149 than 14-89 days after 2nd dose (Odds ratio: 1.6, CI: 1.2-2.3). While estimates of VE against calendar-period-classified infections approximated estimates against WGS-classified infections, calendar-period-based classification was subject to outcome misclassification (35% during Alpha period, 4% during Delta period). Conclusions: These findings suggest that both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While estimates of VE against calendar-period-classified infections mirrored that against WGS-classified infections, our analysis highlights the need for WGS when variants are co-circulating and misclassification is likely.
Keywords	covid19
Language	English
Publishing date	2022-08-26
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.08.25.22278443
Database	COVID19

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Article ; Online: Risk of Sexually Transmitted Zika Virus in a Cohort of Economically Disadvantaged Urban Residents.

Aguilar Ticona, Juan P / Baig, Huma / Nery, Nivison / Doss-Gollin, Simon / Sacramento, Gielson A / Adhikarla, Haritha / Muenker, M Catherine / Wunder, Elsio A / Nascimento, Eduardo J M / Marques, Ernesto T A / Reis, Mitermayer G / Ko, Albert I / Costa, Federico

The Journal of infectious diseases

2020 Volume 224, Issue 5, Page(s) 860–864

Abstract: To understand the disease burden of sexually transmitted Zika virus (ZIKV), we prospectively followed a cohort of 359 adult and adolescent residents of an urban community in Salvador, Brazil, through the 2015 ZIKV epidemic. Later, in 2017, we used a ... ...

Abstract	To understand the disease burden of sexually transmitted Zika virus (ZIKV), we prospectively followed a cohort of 359 adult and adolescent residents of an urban community in Salvador, Brazil, through the 2015 ZIKV epidemic. Later, in 2017, we used a retrospective survey to associate sexual behavior during the epidemic with ZIKV infection as defined by immunoglobulin G3 NS1 enzyme-linked immunosorbent assay. We found that males who engaged in casual sexual encounters during the epidemic were more likely (adjusted odds ratio, 6.2 [95% confidence interval, 1.2-64.1]) to be ZIKV positive, suggesting that specific groups may be at increased risk of sexually transmitted infections.
MeSH term(s)	Adolescent ; Adult ; Female ; Humans ; Male ; Poverty Areas ; Retrospective Studies ; Sexual Behavior ; Sexually Transmitted Diseases, Viral/epidemiology ; Urban Population ; Zika Virus/isolation & purification ; Zika Virus Infection/epidemiology
Language	English
Publishing date	2020-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiab001
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Article ; Online: Kynurenic acid may underlie sex-specific immune responses to COVID-19.

Science signaling

2021 Volume 14, Issue 690

Abstract: Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of ... ...

Abstract	Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA-to-kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males.
MeSH term(s)	Adult ; Aged ; COVID-19/blood ; COVID-19/immunology ; Case-Control Studies ; Cytokine Release Syndrome/blood ; Cytokine Release Syndrome/etiology ; Cytokine Release Syndrome/immunology ; Cytokines/blood ; Cytokines/immunology ; Female ; Humans ; Kynurenic Acid/blood ; Kynurenic Acid/immunology ; Logistic Models ; Male ; Metabolic Networks and Pathways/immunology ; Metabolomics ; Middle Aged ; Multivariate Analysis ; SARS-CoV-2 ; Severity of Illness Index ; Sex Factors ; Signal Transduction/immunology ; Tryptophan/metabolism
Chemical Substances	Cytokines ; Tryptophan (8DUH1N11BX) ; Kynurenic Acid (H030S2S85J)
Language	English
Publishing date	2021-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.abf8483
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection.

PloS one

2021 Volume 16, Issue 3, Page(s) e0248025

Abstract: Introduction: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown ... ...

Abstract	Introduction: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. Methods and findings: We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). Conclusions: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.
MeSH term(s)	Adult ; Anosmia/diagnosis ; Anosmia/epidemiology ; Anosmia/virology ; Asymptomatic Infections/epidemiology ; COVID-19/diagnosis ; COVID-19/epidemiology ; Female ; Health Personnel/statistics & numerical data ; Health Personnel/trends ; Humans ; Male ; Middle Aged ; Prospective Studies ; SARS-CoV-2/pathogenicity ; Self Report ; Smell/physiology ; United States/epidemiology
Language	English
Publishing date	2021-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0248025
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Article ; Online: Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity.

Nature

2021 Volume 600, Issue 7889, Page(s) 523–529

Abstract: The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or ... ...

Abstract	The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination
MeSH term(s)	2019-nCoV Vaccine mRNA-1273/immunology ; Adult ; Aged ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; BNT162 Vaccine/immunology ; COVID-19/epidemiology ; COVID-19/virology ; Female ; Health Personnel/statistics & numerical data ; Humans ; Immunity, Humoral ; Male ; Middle Aged ; Mutation ; Retrospective Studies ; SARS-CoV-2/classification ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; T-Lymphocytes/immunology ; Vaccines, Synthetic/immunology ; mRNA Vaccines/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic ; mRNA Vaccines ; spike protein, SARS-CoV-2 ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-10-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-04085-y
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Article ; Online: Structural factors associated with SARS-CoV-2 infection risk in an urban slum setting in Salvador, Brazil: A cross-sectional survey.

PLoS medicine

2022 Volume 19, Issue 9, Page(s) e1004093

Abstract: Background: The structural environment of urban slums, including physical, demographic, and socioeconomic attributes, renders inhabitants more vulnerable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Yet, little is known ... ...

Abstract	Background: The structural environment of urban slums, including physical, demographic, and socioeconomic attributes, renders inhabitants more vulnerable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Yet, little is known about the specific determinants that contribute to high transmission within these communities. We therefore aimed to investigate SARS-CoV-2 seroprevalence in an urban slum in Brazil. Methods and findings: We performed a cross-sectional serosurvey of an established cohort of 2,041 urban slum residents from the city of Salvador, Brazil between November 2020 and February 2021, following the first Coronavirus Disease 2019 (COVID-19) pandemic wave in the country and during the onset of the second wave. The median age in this population was 29 years (interquartile range [IQR] 16 to 44); most participants reported their ethnicity as Black (51.5%) or Brown (41.7%), and 58.5% were female. The median size of participating households was 3 (IQR 2 to 4), with a median daily per capita income of 2.32 (IQR 0.33-5.15) US Dollars. The main outcome measure was presence of IgG against the SARS-CoV-2 spike protein. We implemented multilevel models with random intercepts for each household to estimate seroprevalence and associated risk factors, adjusting for the sensitivity and specificity of the assay, and the age and gender distribution of our study population. We identified high seroprevalence (47.9%, 95% confidence interval [CI] 44.2% to 52.1%), particularly among female residents (50.3% [95% CI 46.3% to 54.8%] versus 44.6% [95% CI 40.1% to 49.4%] among male residents, p < 0.01) and among children (54.4% [95% CI 49.6% to 59.3%] versus 45.4% [95% CI 41.5% to 49.7%] among adults, p < 0.01). Adults residing in households with children were more likely to be seropositive (48.6% [95% CI 44.8% to 52.3%] versus 40.7% [95% CI 37.2% to 44.3%], p < 0.01). Women who were unemployed and living below the poverty threshold (daily per capita household income <$1.25) were more likely to be seropositive compared to men with the same employment and income status (53.9% [95% CI 47.0% to 60.6%] versus 32.9% [95% CI 23.2% to 44.3%], p < 0.01). Participation in the study was voluntary, which may limit the generalizability of our findings. Conclusions: Prior to the peak of the second wave of the COVID-19 pandemic, cumulative incidence as assessed by serology approached 50% in a Brazilian urban slum population. In contrast to observations from industrialized countries, SARS-CoV-2 incidence was highest among children, as well as women living in extreme poverty. These findings emphasize the need for targeted interventions that provide safe environments for children and mitigate the structural risks posed by crowding and poverty for the most vulnerable residents of urban slum communities.
MeSH term(s)	Adult ; Brazil/epidemiology ; COVID-19/epidemiology ; Child ; Cross-Sectional Studies ; Female ; Humans ; Immunoglobulin G ; Male ; Pandemics ; Poverty Areas ; SARS-CoV-2 ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus
Chemical Substances	Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1004093
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Article ; Online: No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination

Lu-Culligan, Alice / Tabachnikova, Alexandra / Tokuyama, Maria / Lee, Hannah J / Lucas, Carolina / Silva Monteiro, Valter / Muenker, M. Catherine / Mohanty, Subhasis / Huang, Jiefang / Kang, Insoo / Dela Cruz, Charles / Farhadian, Shelli / Campbell, Melissa / Yildirim, Inci / Shaw, Albert / Ko, Albert / Omer, Saad / Iwasaki, Akiko

bioRxiv

Abstract: The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice ... ...

Abstract	The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.
Keywords	covid19
Language	English
Publishing date	2021-12-08
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.12.07.471539
Database	COVID19

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Article: Kynurenic acid underlies sex-specific immune responses to COVID-19.

medRxiv : the preprint server for health sciences

2020

Abstract: Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined ... ...

Abstract	Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined whether the serum metabolome has sex-specificity for immune responses in COVID-19. In males with COVID- 19, kynurenic acid (KA) and a high KA to kynurenine (K) ratio was positively correlated with age, inflammatory cytokines, and chemokines and was negatively correlated with T cell responses, revealing that KA production is linked to immune responses in males. Males that clinically deteriorated had a higher KA:K ratio than those that stabilized. In females with COVID-19, this ratio positively correlated with T cell responses and did not correlate with age or clinical severity. KA is known to inhibit glutamate release, and we observed that serum glutamate is lower in patients that deteriorate from COVID-19 compared to those that stabilize, and correlates with immune responses. Analysis of Genotype-Tissue Expression (GTEx) data revealed that expression of kynurenine aminotransferase, which regulates KA production, correlates most strongly with cytokine levels and aryl hydrocarbon receptor activation in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes, in COVID-19 infection.
Keywords	covid19
Language	English
Publishing date	2020-09-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.09.06.20189159
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