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1.
Signal Transduct Target Ther ; 6(1): 342, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415923

ABSTRACT

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.


Subject(s)
COVID-19 , Carrier State/immunology , Lymphocytes/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Transcriptome/immunology , Adolescent , Adult , COVID-19/genetics , COVID-19/immunology , Female , Humans , Male , Middle Aged , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/genetics
2.
Clin Infect Dis ; 72(10): e652-e654, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232192

ABSTRACT

Coronavirus disease 2019 (COVID-19) patients exhaled millions of severe acute respiratory syndrome coronavirus 2 RNA copies per hour, which plays an important role in COVID-19 transmission. Exhaled breath had a higher positive rate (26.9%, n = 52) than surface (5.4%, n = 242) and air (3.8%, n = 26) samples.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Respiratory System
3.
Cytokine ; 142: 155500, 2021 06.
Article in English | MEDLINE | ID: covidwho-1141708

ABSTRACT

We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity.


Subject(s)
COVID-19/blood , Chemokine CXCL10/blood , Interleukin-7/blood , SARS-CoV-2/metabolism , Severity of Illness Index , Female , Humans , Male , Middle Aged
4.
mBio ; 11(5)2020 10 13.
Article in English | MEDLINE | ID: covidwho-868276

ABSTRACT

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.


Subject(s)
Animals, Zoo/virology , Betacoronavirus/physiology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Pandemics/veterinary , Panthera/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/veterinary , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Genome, Viral/genetics , Haplotypes , Humans , New York City/epidemiology , One Health , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Zoonoses/epidemiology , Zoonoses/transmission , Zoonoses/virology
7.
JAMA Intern Med ; 180(12): 1665-1671, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-738931

ABSTRACT

Importance: Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective: To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants: This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures: SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results: Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance: In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.


Subject(s)
COVID-19 , Communicable Disease Control/methods , Community-Acquired Infections , Motor Vehicles/statistics & numerical data , SARS-CoV-2 , Transportation/methods , Air Pollution , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , China/epidemiology , Cohort Studies , Community-Acquired Infections/diagnosis , Community-Acquired Infections/epidemiology , Community-Acquired Infections/prevention & control , Community-Acquired Infections/transmission , Disease Transmission, Infectious/prevention & control , Disease Transmission, Infectious/statistics & numerical data , Female , Humans , Male , Middle Aged , Risk Assessment , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
8.
Crit Care ; 24(1): 422, 2020 07 13.
Article in English | MEDLINE | ID: covidwho-641221

ABSTRACT

An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1-7), and the ACE2/angiotensin-(1-7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1-7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1-7)/MAS may help attenuate organ injuries. SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.


Subject(s)
Coronavirus Infections/enzymology , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/enzymology , Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Pandemics
9.
Cell Rep ; 32(3): 107918, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-625076

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Receptors, Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/immunology , COVID-19 , Coronavirus Infections/therapy , Epitope Mapping , Epitopes/immunology , Humans , Immunologic Memory/immunology , Neutralization Tests , Pandemics , Pneumonia, Viral/therapy , Protein Domains/immunology , SARS-CoV-2
10.
Emerg Infect Dis ; 26(6): 1266-1273, 2020 06.
Article in English | MEDLINE | ID: covidwho-324432

ABSTRACT

The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Animals , Betacoronavirus/genetics , Betacoronavirus/physiology , COVID-19 , Cell Line , Chlorocebus aethiops , Genome, Viral , Humans , Nasopharynx/virology , Oropharynx/virology , Pandemics , SARS-CoV-2 , Vero Cells , Viral Tropism , Virus Replication , Washington
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