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1.
Nat Immunol ; 23(6): 960-970, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1873528

ABSTRACT

The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate a large panel of human broadly neutralizing antibodies (bnAbs) to sarbecoviruses. Many of these bnAbs are remarkably effective in neutralizing a diversity of sarbecoviruses and against most SARS-CoV-2 VOCs, including the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor-binding domain (RBD). Consistent with targeting of conserved sites, select RBD bnAbs exhibited protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model in vivo. These bnAbs provide new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective design of pan-sarbecovirus vaccines.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , Humans , Spike Glycoprotein, Coronavirus
2.
Viruses ; 14(5)2022 05 14.
Article in English | MEDLINE | ID: covidwho-1855821

ABSTRACT

The authors report on a possible direct exposure to SARS-CoV-2 from a COVID-19-positive individual to an adult horse. The individual, diagnosed with COVID-19 (Delta B.1.617.2), had daily contact to her two horses prior to and during the development of clinical disease. None of the two horses developed abnormal clinical signs or had detectable SARS-CoV-2 in blood, nasal secretion, or feces via RT-qPCR. However, one of the two horses showed close temporal seroconversion to SARS-CoV-2 using a protein-based ELISA and the plaque reduction neutralization test. The results suggest that horses can become silently infected with SARS-CoV-2 following close contact with humans infected with SARS-CoV-2. As a precautionary measure, humans infected with SARS-CoV-2 should avoid close contact with equids and other companion animals during the time of their illness to prevent viral transmission.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/veterinary , Enzyme-Linked Immunosorbent Assay , Female , Horses , Seroconversion
4.
Sci Transl Med ; 14(637): eabi9215, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1673344

ABSTRACT

Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and as templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from a CoV disease 2019 (COVID-19) convalescent donor that exhibits broad reactivity with human ß-CoVs. Here, we showed that CC40.8 targets the conserved S2 stem helix region of the CoV spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem peptide at 1.6-Å resolution and found that the peptide adopted a mainly helical structure. Conserved residues in ß-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. Furthermore, we noted that CC40.8-like bnAbs are relatively rare in human COVID-19 infection, and therefore, their elicitation may require rational structure-based vaccine design strategies. Overall, our study describes a target on ß-CoV spike proteins for protective antibodies that may facilitate the development of pan-ß-CoV vaccines.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Animals , Antibodies, Neutralizing/metabolism , Antibodies, Viral , COVID-19/immunology , Humans , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
5.
Cell Host Microbe ; 30(3): 388-399.e3, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1670319

ABSTRACT

Both SARS-CoV-2 infections and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of 2 pools of experimentally defined SARS-CoV-2 T cell epitopes that, in combination with spike, were used to discriminate 4 groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status. The overall T cell-based classification accuracy was 89.2% and 88.5% in the experimental and validation cohorts. This scheme was applicable to different mRNA vaccines and different lengths of time post infection/post vaccination and yielded increased accuracy when compared to serological readouts. T cell responses from breakthrough infections were also studied and effectively segregated from vaccine responses, with a combined performance of 86.6% across all 239 subjects from the 5 groups. We anticipate that a T cell-based immunodiagnostic scheme to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccinations and for establishing SARS-CoV-2 correlates of protection.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/diagnosis , Epitopes, T-Lymphocyte , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination
6.
Yonsei Med J ; 62(11): 961-968, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1553997

ABSTRACT

Since the COVID-19 pandemic first began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has continuously evolved with many variants emerging across the world. These variants are categorized as the variant of interest (VOI), variant of concern (VOC), and variant under monitoring (VUM). As of September 15, 2021, there are four SARS-CoV-2 lineages designated as the VOC (alpha, beta, gamma, and delta variants). VOCs have increased transmissibility compared to the original virus, and have the potential for increasing disease severity. In addition, VOCs exhibit decreased susceptibility to vaccine-induced and infection-induced immune responses, and thus possess the ability to reinfect previously infected and recovered individuals. Given their ability to evade immune responses, VOC are less susceptible to monoclonal antibody treatments. VOCs can also impact the effectiveness of mRNA and adenovirus vector vaccines, although the currently authorized COVID-19 vaccines are still effective in preventing infection and severe disease. Current measures to reduce transmission as well as efforts to monitor and understand the impact of variants should be continued. Here, we review the molecular features, epidemiology, impact on transmissibility, disease severity, and vaccine effectiveness of VOCs.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19 Vaccines , Humans , Pandemics , SARS-CoV-2
7.
Cell ; 184(25): 6022-6036.e18, 2021 12 09.
Article in English | MEDLINE | ID: covidwho-1536466

ABSTRACT

Viral-deletion mutants that conditionally replicate and inhibit the wild-type virus (i.e., defective interfering particles, DIPs) have long been proposed as single-administration interventions with high genetic barriers to resistance. However, theories predict that robust, therapeutic DIPs (i.e., therapeutic interfering particles, TIPs) must conditionally spread between cells with R0 >1. Here, we report engineering of TIPs that conditionally replicate with SARS-CoV-2, exhibit R0 >1, and inhibit viral replication 10- to 100-fold. Inhibition occurs via competition for viral replication machinery, and a single administration of TIP RNA inhibits SARS-CoV-2 sustainably in continuous cultures. Strikingly, TIPs maintain efficacy against neutralization-resistant variants (e.g., B.1.351). In hamsters, both prophylactic and therapeutic intranasal administration of lipid-nanoparticle TIPs durably suppressed SARS-CoV-2 by 100-fold in the lungs, reduced pro-inflammatory cytokine expression, and prevented severe pulmonary edema. These data provide proof of concept for a class of single-administration antivirals that may circumvent current requirements to continually update medical countermeasures against new variants.


Subject(s)
COVID-19/drug therapy , Virus Replication/drug effects , Animals , Antiviral Agents/pharmacology , COVID-19/metabolism , Cell Line , Chlorocebus aethiops , Culture Media, Conditioned/pharmacology , Drug Delivery Systems/methods , Epithelial Cells , Humans , Male , Mesocricetus , Nanoparticles/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Vero Cells
8.
Clin Infect Dis ; 73(9): 1717-1721, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501059

ABSTRACT

As of March 2021, coronavirus disease 2019 (COVID-19) had caused more than 123 million infections and almost 3 million deaths worldwide. Dramatic advances have been made in vaccine development and nonpharmaceutical interventions to stop the spread of infection. However, treatments to stop disease progression are limited. A wide variety of "repurposed" drugs evaluated for treatment of COVID-19 have had little or no benefit. More recently, intravenous monoclonal antibody (mAb) combinations have been authorized by the US Food and Drug Administration for emergency use for outpatients with mild to moderate COVID-19 including some active against emerging severe acute respiratory syndrome coronavirus 2 variants of concern. Easier to administer therapeutics including intramuscular and subcutaneous mAbs and oral antivirals are in clinical trials. Reliable, safe, effective COVID-19 treatment for early infection in the outpatient setting is of urgent and critical importance. Availability of such treatment should lead to reduced progression of COVID-19.


Subject(s)
COVID-19 , Pharmaceutical Preparations , COVID-19/drug therapy , Humans , Outpatients , SARS-CoV-2
9.
Open Forum Infect Dis ; 7(8): ofaa325, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1387984

ABSTRACT

RNA viruses (eg, Zika, Ebola, HIV) are often shed in male genital secretions. We evaluated the presence and level of SARS-CoV-2 RNA in semen, nasal secretion, and saliva collected after confirmed infection. SARS-CoV-2 RNA was not detected in semen 6-17 days after the onset of symptoms despite concomitant shedding in oral secretions.

10.
Science ; 371(6529)2021 02 05.
Article in English | MEDLINE | ID: covidwho-1309798

ABSTRACT

Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunologic Memory , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , United States , Young Adult
11.
Cell Rep Med ; 2(7): 100355, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1294298

ABSTRACT

The emergence of SARS-CoV-2 variants with evidence of antibody escape highlight the importance of addressing whether the total CD4+ and CD8+ T cell recognition is also affected. Here, we compare SARS-CoV-2-specific CD4+ and CD8+ T cells against the B.1.1.7, B.1.351, P.1, and CAL.20C lineages in COVID-19 convalescents and in recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. The total reactivity against SARS-CoV-2 variants is similar in terms of magnitude and frequency of response, with decreases in the 10%-22% range observed in some assay/VOC combinations. A total of 7% and 3% of previously identified CD4+ and CD8+ T cell epitopes, respectively, are affected by mutations in the various VOCs. Thus, the SARS-CoV-2 variants analyzed here do not significantly disrupt the total SARS-CoV-2 T cell reactivity; however, the decreases observed highlight the importance for active monitoring of T cell reactivity in the context of SARS-CoV-2 evolution.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Young Adult
12.
EBioMedicine ; 68: 103390, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1267655

ABSTRACT

BACKGROUND: Coronavirus Disease 2019 (Covid-19) continues to challenge the limits of our knowledge and our healthcare system. Here we sought to define the host immune response, a.k.a, the "cytokine storm" that has been implicated in fatal COVID-19 using an AI-based approach. METHOD: Over 45,000 transcriptomic datasets of viral pandemics were analyzed to extract a 166-gene signature using ACE2 as a 'seed' gene; ACE2 was rationalized because it encodes the receptor that facilitates the entry of SARS-CoV-2 (the virus that causes COVID-19) into host cells. An AI-based approach was used to explore the utility of the signature in navigating the uncharted territory of Covid-19, setting therapeutic goals, and finding therapeutic solutions. FINDINGS: The 166-gene signature was surprisingly conserved across all viral pandemics, including COVID-19, and a subset of 20-genes classified disease severity, inspiring the nomenclatures ViP and severe-ViP signatures, respectively. The ViP signatures pinpointed a paradoxical phenomenon wherein lung epithelial and myeloid cells mount an IL15 cytokine storm, and epithelial and NK cell senescence and apoptosis determine severity/fatality. Precise therapeutic goals could be formulated; these goals were met in high-dose SARS-CoV-2-challenged hamsters using either neutralizing antibodies that abrogate SARS-CoV-2•ACE2 engagement or a directly acting antiviral agent, EIDD-2801. IL15/IL15RA were elevated in the lungs of patients with fatal disease, and plasma levels of the cytokine prognosticated disease severity. INTERPRETATION: The ViP signatures provide a quantitative and qualitative framework for titrating the immune response in viral pandemics and may serve as a powerful unbiased tool to rapidly assess disease severity and vet candidate drugs. FUNDING: This work was supported by the National Institutes for Health (NIH) [grants CA151673 and GM138385 (to DS) and AI141630 (to P.G), DK107585-05S1 (SD) and AI155696 (to P.G, D.S and S.D), U19-AI142742 (to S. C, CCHI: Cooperative Centers for Human Immunology)]; Research Grants Program Office (RGPO) from the University of California Office of the President (UCOP) (R00RG2628 & R00RG2642 to P.G, D.S and S.D); the UC San Diego Sanford Stem Cell Clinical Center (to P.G, D.S and S.D); LJI Institutional Funds (to S.C); the VA San Diego Healthcare System Institutional funds (to L.C.A). GDK was supported through The American Association of Immunologists Intersect Fellowship Program for Computational Scientists and Immunologists. ONE SENTENCE SUMMARY: The host immune response in COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Antiviral Agents/administration & dosage , COVID-19/genetics , Gene Expression Profiling/methods , Interleukin-15/genetics , Receptors, Interleukin-15/genetics , Virus Diseases/genetics , Animals , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/pharmacology , Antiviral Agents/pharmacology , Artificial Intelligence , Autopsy , COVID-19/drug therapy , COVID-19/immunology , Cricetinae , Cytidine/administration & dosage , Cytidine/analogs & derivatives , Cytidine/pharmacology , Databases, Genetic , Disease Models, Animal , Gene Regulatory Networks/drug effects , Genetic Markers/drug effects , Humans , Hydroxylamines/administration & dosage , Hydroxylamines/pharmacology , Interleukin-15/blood , Lung/immunology , Mesocricetus , Pandemics , Receptors, Interleukin-15/blood , Virus Diseases/immunology
14.
Nat Commun ; 12(1): 2938, 2021 05 19.
Article in English | MEDLINE | ID: covidwho-1236086

ABSTRACT

Pre-existing immunity to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, induced from natural infection or vaccination. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. Here we compare serum antibody and memory B cell responses to coronavirus spike proteins from pre-pandemic and SARS-CoV-2 convalescent donors using binding and functional assays. We show weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we find evidence of pre-existing cross-reactive memory B cells that are activated during SARS-CoV-2 infection. Monoclonal antibodies show varying degrees of cross-reactivity with betacoronaviruses, including SARS-CoV-1 and endemic coronaviruses. We identify one cross-reactive neutralizing antibody specific to the S2 subunit of the S protein. Our results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Cross Protection/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , B-Lymphocytes/immunology , Cross Reactions/immunology , Female , Humans , Immunologic Memory/immunology , Male
15.
Contemp Clin Trials ; 103: 106330, 2021 04.
Article in English | MEDLINE | ID: covidwho-1101134

ABSTRACT

BACKGROUND AND AIMS: Retrospective studies have shown that angiotensin-converting-enzyme (ACE) inhibitors are associated with a reduced risk of complications and mortality in persons with novel coronavirus disease 2019 (COVID-19). Thus, we aimed to examine the efficacy of ramipril, an ACE-inhibitor, in preventing ICU admission, mechanical ventilation and/or mortality while also minimizing the risk of transmission and use of personal protective equipment (PPE). METHODS: RAMIC is a multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial comparing the efficacy of treatment with ramipril 2.5 mg orally daily compared to placebo for 14 days. The study population includes adult patients with COVID-19 who were admitted to a hospital or assessed in an emergency department or ambulatory clinic. Key exclusion criteria include ICU admission or need for mechanical ventilation at screening, use of an ACE inhibitor or angiotensin-receptor-II blocker within 7 days, glomerular filtration rate < 40 mL/min or a systolic blood pressure (BP) < 100 mmHg or diastolic BP < 65 mmHg. Patients are randomized 2:1 to receive ramipril (2.5 mg) or placebo daily. Informed consent and study visits occur virtually to minimize the risk of SARS-CoV-2 transmission and preserve PPE. The primary composite endpoint of ICU admission, invasive mechanical ventilation and death are adjudicated virtually. CONCLUSIONS: RAMIC is designed to assess the efficacy of treatment with ramipril for 14 days to decrease ICU admission, mechanical ventilator use and mortality in patients with COVID-19 and leverages virtual study visits and endpoint adjudication to mitigate risk of infection and to preserve PPE (ClinicalTrials.gov, NCT04366050).


Subject(s)
COVID-19 , Ramipril , Adult , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Biomarkers/analysis , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , COVID-19/transmission , Critical Care/statistics & numerical data , Disease Transmission, Infectious/prevention & control , Double-Blind Method , Female , Humans , Male , Mortality , Ramipril/administration & dosage , Ramipril/adverse effects , Randomized Controlled Trials as Topic , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Treatment Outcome
16.
Cell Rep Med ; 2(2): 100204, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-1057492

ABSTRACT

T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens and precisely measure virus-specific CD4+ and CD8+ T cells, we study epitope-specific T cell responses of 99 convalescent coronavirus disease 2019 (COVID-19) cases. The SARS-CoV-2 proteome is probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of human leukocyte antigen (HLA) alleles for class II responses. For HLA class I, we study an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identify several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance are observed, which differ for CD4+ T cells, CD8+ T cells, and antibodies. The class I and class II epitopes are combined into epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4+ and CD8+ T cells.

17.
Open Forum Infect Dis ; 7(11): ofaa305, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1024129

ABSTRACT

The COVID- 19 pandemic has showcased the field of Infectious Diseases (ID). We used Google Trends to find that this newfound attention has led to higher interest in ID training.

19.
JAMA ; 324(16): 1651-1669, 2020 10 27.
Article in English | MEDLINE | ID: covidwho-865967

ABSTRACT

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/prevention & control , AIDS-Related Opportunistic Infections/drug therapy , Age Factors , Anti-Retroviral Agents/economics , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Drug Administration Schedule , Drug Costs , Drug Resistance, Viral/genetics , Drug Substitution/standards , Drug Therapy, Combination/methods , Female , HIV Infections/blood , HIV Infections/diagnosis , Humans , International Agencies , Male , Pandemics , Pneumonia, Viral/epidemiology , Polypharmacy , Pre-Exposure Prophylaxis/methods , Pregnancy , Pregnancy Complications, Infectious/drug therapy , RNA, Viral/blood , SARS-CoV-2 , Societies, Medical , United States , Viral Load/genetics
20.
bioRxiv ; 2020 Sep 23.
Article in English | MEDLINE | ID: covidwho-807603

ABSTRACT

Pre-existing immune responses to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, either induced in natural infection or through vaccination. Such consequences are well established in the influenza and flavivirus fields. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. We compared serum antibody and memory B cell responses to coronavirus spike (S) proteins from pre-pandemic and SARS-CoV-2 convalescent donors using a series of binding and functional assays. We found weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we found stronger evidence of pre-existing cross-reactive memory B cells that were activated on SARS-CoV-2 infection. Monoclonal antibodies (mAbs) isolated from the donors showed varying degrees of cross-reactivity with betacoronaviruses, including SARS and endemic coronaviruses. None of the cross-reactive mAbs were neutralizing except for one that targeted the S2 subunit of the S protein. The results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2.

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