Antibody Response Following SARS-CoV-2 Infection and Implications for Immunity: A Rapid Living Review

 Evidence suggests that the majority of adults develop detectable levels of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies following infection with SARS-CoV-2 (moderate strength of evidence* [SoE]).  IgM levels peak approximately 20 days after symptom onset or RT-PCR diagnosis and subsequently decline. IgG levels peak approximately 25 days after symptom onset or RT-PCR diagnosis and may remain detectable for at least 120 days (moderate SoE*).  Almost all adults develop neutralizing antibodies in response to SARS-CoV-2 infection, and these antibodies may remain detectable for at least 152 days (low SoE*).  A small percentage of people do not develop antibodies in response to SARS-CoV-2 infection for reasons that are largely unclear but may be related to less severe disease or absence of symptoms.  Antibody prevalence does not appear to vary by age or sex, but older age may be associated with higher antibody levels (low SoE*). Non-White race may be associated with higher antibody prevalence and levels (low SoE*). COVID-19 severity and presence of symptoms may also be associated with higher antibody prevalence or levels (low SoE*). More evidence is needed to draw stronger conclusions regarding how the antibody response varies by patient characteristics and disease factors.  Studies to date have not established the relationship between the development of antibodies after RT-PCR-diagnosed SARS-CoV-2 infection and the risk of reinfection. Studies based on index serologic testing suggest that the presence of antibodies is associated with a lower risk of a subsequent positive SARS-CoV-2 RT-PCR test.

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Can we predict antibody responses in SARS-CoV-2? A cohort analysis

10.1101/2021.03.15.21253267 ◽

2021 ◽

Author(s):

Mary Gaeddert ◽

Philip Kitchen ◽

Tobias Broger ◽

Stefan Weber ◽

Ralf Bartenschlager ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Severe Disease ◽

Cohort Analysis ◽

Antibody Responses ◽

High Antibody ◽

Igg Antibodies ◽

Rt Pcr ◽

Median Increase ◽

Antibody Titers

AbstractBackgroundAfter infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.MethodsWe recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.Results281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR −0.3-1.7). Six participants with follow-up nAbs all had titers ≤ 1:80.ConclusionsWhile age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.

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LB2. Safety and Efficacy of Combination SARS-CoV-2 Monoclonal Neutralizing Antibodies (mAb) BRII-196 and BRII-198 in Non-Hospitalized COVID-19 Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1643 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S807-S808

Author(s):

Teresa H Evering ◽

Mark Giganti ◽

Kara W Chew ◽

Michael Hughes ◽

Carlee Moser ◽

...

Keyword(s):

High Risk ◽

Symptom Onset ◽

Interim Analysis ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Panel Member ◽

The Philippines ◽

Research Support ◽

Review Panel ◽

Research Grant

Abstract Background SARS-CoV-2 continues to spread and the development of safe and effective therapeutics for the prevention of severe disease remains a priority. BRII-196 and BRII-198 are non-competing anti-SARS-CoV-2 mAbs with YTE triple amino acid substitution in Fc to extend half-life and reduce receptor binding, that are being studied for treatment of COVID-19 in the ACTIV-2 Trial, sponsored by NIAID and led by ACTG. Methods ACTIV-2 evaluates safety/efficacy of investigational agents for treatment of non-hospitalized adults with mild-moderate COVID-19 under a randomized, blinded, controlled adaptive platform. BRII-196/BRII-198 (1000 mg each) as a single dose given as sequential infusions, or placebo to those at high risk of clinical progression (i.e., age ≥ 60 years or presence of other medical conditions) within 10 days of symptom onset and positive test for SARS-CoV-2. The primary endpoint was hospitalization and/or death through day 28. We report Phase 3 BRII-196/BRII-198 trial results per DSMB recommendation following an interim analysis. Results Between January and July 2021, 837 participants (418 active, 419 placebo) from sites in the US (66%), Brazil, South Africa, Mexico, Argentina and the Philippines were randomized and received study product at time of emerging variants. Median age 49 years (Q1, Q3: 39, 58), 51% female, 17% Black/African-American and 49% Hispanic/Latino, with median 6 days from symptom onset. At interim analysis 71% and 97% had a day 28 and 7 visit, respectively. For all available data at interim review, BRII-196/BRII-198 compared to placebo had fewer hospitalizations (12 vs. 45) and deaths (1 vs. 9). At day 28 of follow-up, there was an estimated 78% reduction in hospitalization and/or death (2.4 vs. 11.1%), relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001 (nominal one-sided). Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8% vs. 13.4%) with no severe infusion reactions or drug related serious AEs. Conclusion BRII-196/BRII-198 was safe, well-tolerated, and demonstrated significant reduction compared to placebo in the risk of hospitalization and/or death among adults with mild-moderate COVID-19 at high risk for progression to severe disease. Disclosures Kara W. Chew, MD, MS, Amgen (Individual(s) Involved: Self): Grant/Research Support; Merck Sharp & Dohme (Individual(s) Involved: Self): Grant/Research Support David Alain Wohl, MD, Gilead Sciences (Individual(s) Involved: Self): Advisor or Review Panel member, Consultant, Research Grant or Support, Scientific Research Study Investigator; Janssen (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support; ViiV (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV (Consultant, Research Grant or Support) David A. Margolis, MD MPH, Brii Biosciences (Employee) Courtney Fletcher, Pharm.D., National Institute of Allergy and Infectious Diseases, NIH (Grant/Research Support) Davey Smith, M.D., Linear Therapies, Matrix Biomed, Bayer (Consultant, Shareholder) Eric Daar, Gilead (Consultant, Grant/Research Support)Merck (Consultant)ViiV (Consultant, Grant/Research Support)

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512. Does Time From COVID-19 Symptom Onset to Administration of Anti-spike Protein Monoclonal Antibody Predict Response?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.711 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S358-S358

Author(s):

Savanna SanFilippo ◽

Brynna Crovetto ◽

Marc Milano ◽

John Bucek ◽

Ronald G Nahass ◽

...

Keyword(s):

Monoclonal Antibody ◽

Hospital Admission ◽

Symptom Onset ◽

Severe Disease ◽

Admission Rate ◽

Patient Characteristics ◽

Research Support ◽

Early Administration ◽

Hospital Admission Rate ◽

Patient Reported

Abstract Background Casirivimab/imdevimab is a monoclonal antibody (mAb) cocktail with emergency use authorization for mild-to-moderate coronavirus disease 2019 (Covid-19) in patients at high risk for severe disease progression and/or hospitalization. Little is known about the importance of early administration of this product. The objective of this study was to determine if early administration (within 3 days of symptom onset) of casirivimab/imdevimab is associated with better outcomes. Methods Single-center, retrospective cohort study including all consecutive patients who received casirivimab/imdevimab at our institution through May 2021. The primary outcome was 30-day post-infusion hospital admission rate in patients who received mAb ≥ 3 days (later) or < 3 days (early) in relation to patient reported symptom onset. Secondary outcomes included any hospital revisit within 30-days. Adverse events were also captured. Chi-square and independent samples t-test were used to compare categorical and continuous data, respectively. Multivariable logistic regression was used to adjust for confounders. Results 270 patients met the inclusion criteria and were included in the analysis. There were 80 patients with early administration and 190 with later administration. Baseline characteristics for both groups were similar. Mean age was approximately 64 years and BMI 31 mg/m2. Table 1 provides a summary of patient characteristics. Late and early administration of casirivimab/imdevimab were similar in terms of hospital admission for any therapy related failure within 30 days of mAb administration after adjusting for age and Charlson comorbidity index (3.7% vs. 7.5%; adjusted odds ratio 0.69, 95% confidence interval, 0.20 – 2.39; p=0.561). Similarly, there were no significant differences in any hospital revisit. Conclusion We did not find any difference in outcomes between early and late administration of casirivimab/imdevimab. Disclosures Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker's Bureau)Merck (Grant/Research Support, Speaker's Bureau)

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SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus

Wellcome Open Research ◽

10.12688/wellcomeopenres.16002.2 ◽

2020 ◽

Vol 5 ◽

pp. 181

Author(s):

Monique I. Andersson ◽

Carolina V. Arancibia-Carcamo ◽

Kathryn Auckland ◽

J. Kenneth Baillie ◽

Eleanor Barnes ◽

...

Keyword(s):

Symptom Onset ◽

Severe Disease ◽

Acute Infection ◽

Laboratory Diagnosis ◽

Blood Products ◽

Rt Pcr ◽

Serum Samples ◽

Blood Samples ◽

Viral Loads ◽

Clinical Cohort

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

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CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease Following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology

Vaccines ◽

10.3390/vaccines9111346 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1346

Author(s):

Jennifer K. DeMarco ◽

Joshua M. Royal ◽

William E. Severson ◽

Jon D. Gabbard ◽

Steve Hume ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Potential Role ◽

Vaccine Candidate ◽

Severe Disease ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Receptor Binding Domain ◽

Symptomatic Disease ◽

Human Igg1

We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.

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Antibody Response Against Sars-Cov-2 in Convalescent Plasma Donors: Preliminary Results from a Single Center in Midwest Brazil

Blood ◽

10.1182/blood-2020-143177 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 3-4

Author(s):

Maria do Rosario Ferraz Roberti ◽

Tiago Paiva Prudente ◽

Renato Gomes Castro ◽

Marcos Antonio Candido ◽

Roberta Luiza Rodrigues ◽

...

Keyword(s):

Antibody Response ◽

Allergy Clin Immunol ◽

Symptom Onset ◽

Conflicts Of Interest ◽

Time Interval ◽

Sample Collection ◽

Rt Pcr ◽

Upper Airways ◽

Serological Tests ◽

Allergy Clin

In March 2020, COVID-19 was declared a pandemic by the WHO. Since then, efforts have been made to increase our knowledge of the disease. The convalescent plasma (CP) donation involves a series of criteria for donor eligibility, such as pre-donation and serological tests. Currently, the antibody response against SARS-CoV-2 remains poorly understood and the usefulness of serological tests is unclear (Long, et al. Nature Medicine, 2020). Based on donor eligibility, one can better assess the antibody response to SARS-CoV-2 from post-infection candidates. This is an observational, prospective study, without intervention. From 06/26/2020 to 07/31/2020, serological data of candidates for CP donation were collected. Recovered COVID-19 patients who had been previously tested were interviewed. RT-PCR and serological test (chemiluminescence immunoassays) for SARS-CoV-2 were carried out to verify their eligibility for CP collection. The data were related to the time of the onset of symptoms and the collection of the material. Subjects with non-detectable RT-PCR and reagent IgG were considered eligible. Reference values were IgM > 1.2 AU/mL and IgG > 1.4 AU/mL. The characteristics of the candidates are summarized in Table 1. Of 234 interviewed subjects, 70 were screened for pre-collection tests, 49 were male. The average age was 36 (20 - 57). After serological screening, 44/70 (62.8%) were considered eligible for CP donation. The reasons for ineligibility were: 17/70 (24.3%) non-reagent IgG, 4/70 (5.7%) with detectable RT-PCR and 5/70 (7.1%) due to reasons in clinical screening. The median between the onset of symptoms and the serology sample collection was 32.5 (21 - 77) days, (IQR 28.75 to 37.25). Those who were more likely to be eligible to donate were the subjects who had a longer time interval between the symptoms onset and the sample collection (p <0.012). Although viral clearance in the upper airways is expected from the 10th day of symptom onset, only 50% of patients will have an undetectable test (Özçürümez, et al. J Allergy Clin Immunol. 2020). In our sample, 5.7% (4/70) of the subjects had detectable RT-PCR, which can represent residual viral genome and not active infection. We observed that 20% of the subjects samples were non-reagent. Those who were tested up to the 21st of the onset of symptoms might not have had seroconversion yet. For those tested after the 28th day, we can infer that the antibodies had already been cleared. Some authors state that patients who had mild infections may react with less antibodies (Özçürümez, et al. J Allergy Clin Immunol. 2020), which could explain this fact. Likewise, it was not possible to relate serological titers to the severity of the disease, as this was not one of the selection criteria.In 40/70 donors (57.2%) IgM remained above 1.2 AU / mL after the 21st day of symptom onset. Interestingly, 2 of these had only reagent IgM after the 36th day of symptom onset. Most subjects who had reagent IgM after the 21st of symptoms also had reagent IgG. We inferred that they were in a vigorous convalescence phase. In addition, 75.7% of the subjects presented reagent IgG regardless of the date of onset of symptoms. Most of them had both reagent IgM and IgG. Only one donor's (1.4%) IgM and IgG were non-reagent 21 days after the onset of symptoms. As we did not collect serial samples, we could not verify the average amount of days for seroconversion to take place. Some authors recommend that the single collection should occur at least 21 days after the onset of symptoms, so seroconversion is observed (Deeks, et al., Cochrane Database Syst Rev. 2020). In our sample, 4 donors (5%) collected the samples on the 21st day after the symptom onset. Of these, 3 had seroconversion, 2 with IgM and IgG, 1 with IgG and 1 with reagent IgM. The values suggest that the subjects who could donate CP were those that presented a longer time interval between the onset of symptoms and the blood sample collection, in comparison to those who could not (p=0,012 and 0,409, respectively). The median of days between symptom onset and serology testing was also higher in the non-eligible group. Besides, the eligible group had a higher average concentration of IgM and IgG compared to the non-eligible one. In conclusion, regarding the serological criteria, about 25% of the studied population could not donate CP. Although a single serology sample collection after the 21st day of symptom onset is recommended, only 1 candidate did not show seroconversion. Disclosures No relevant conflicts of interest to declare.

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Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis

Kidney360 ◽

10.34067/kid.0004372021 ◽

2021 ◽

Vol 2 (12) ◽

pp. 1917-1927

Author(s):

Ana Cecilia Bardossy ◽

Lauren Korhonen ◽

Sabrina Schatzman ◽

Paige Gable ◽

Carolyn Herzig ◽

...

Keyword(s):

Symptom Onset ◽

Neutralizing Antibodies ◽

Clinical Course ◽

Rt Pcr ◽

Convenience Sample ◽

Content Type ◽

Specific Antibodies ◽

Viral Culture ◽

Maintenance Dialysis ◽

Dialysis Facilities

BackgroundPatients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity.MethodsFrom August to November 2020, we enrolled patients on maintenance dialysis with SARS-CoV-2 infections from outpatient dialysis facilities in Atlanta, Georgia. We followed participants for approximately 42 days. We assessed COVID-19 symptoms and collected specimens. Oropharyngeal (OP), anterior nasal (AN), and saliva (SA) specimens were tested for the presence of SARS-CoV-2 RNA, using RT-PCR, and sent for viral culture. Serology, including neutralizing antibodies, was measured in blood specimens.ResultsFifteen participants, with a median age of 58 (range, 37‒77) years, were enrolled. Median duration of RT-PCR positivity from diagnosis was 18 days (interquartile range [IQR], 8‒24 days). Ten participants had at least one, for a total of 41, positive RT-PCR specimens ≥10 days after symptoms onset. Of these 41 specimens, 21 underwent viral culture; one (5%) was positive 14 days after symptom onset. Thirteen participants developed SARS-CoV-2–specific antibodies, 11 of which included neutralizing antibodies. RT-PCRs remained positive after seroconversion in eight participants and after detection of neutralizing antibodies in four participants; however, all of these samples were culture negative.ConclusionsPatients with ESKD on maintenance dialysis remained persistently and intermittently SARS-CoV-2–RT-PCR positive. However, of the 15 participants, only one had infectious virus, on day 14 after symptom onset. Most participants mounted an antibody response, including neutralizing antibodies. Participants continued having RT-PCR–positive results in the presence of SARS-CoV-2–specific antibodies, but without replication-competent virus detected.

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COVID-BioB Cohort Study: the neutralizing antibody response to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for virus control and survival

10.1101/2021.02.17.21251929 ◽

2021 ◽

Author(s):

Stefania Dispinseri ◽

Massimiliano Secchi ◽

Maria Franca Pirillo ◽

Monica Tolazzi ◽

Martina Borghi ◽

...

Keyword(s):

Antibody Response ◽

Symptom Onset ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Therapeutic Interventions ◽

Critical Conditions ◽

Specific Response ◽

Increased Risk ◽

Antibody Titers ◽

Flu Virus

ABSTRACTUnderstanding how antibody to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches to prevent fatal COVID-19 illness and vaccines. Here, we profile the antibody response of 162 well-characterized COVID-19 symptomatic patients followed longitudinally for up to eight months from symptom onset. Using two newly developed assays we detect SARS-CoV-2 neutralization and antibodies binding to Spike antigens and nucleoprotein as well as to Spike S2 antigen of seasonal beta-coronaviruses, and to hemagglutinin of the H1N1 flu virus. Presence of neutralizing antibodies withing the first weeks from symptom onset correlates with time to a negative swab result (p=0.002) while lack of neutralization with an increased risk of a fatal disease outcome (HR 2.918, 95%CI 1.321-6.449; p=0.008). Neutralizing antibody titers progressively drop after 5-8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities. IgG to Spike antigens are the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporary boosted and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Thus, a compromised immune response to the Spike rather than an enhanced one is a major trait of patients with critical conditions. Patients should be promptly identified and immediately start therapeutic interventions aimed at restoring their immunity.

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SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus

10.1101/2020.05.21.20105486 ◽

2020 ◽

Cited By ~ 5

Author(s):

Monique I Andersson ◽

Carolina V Arancibia-Cárcamo ◽

Kathryn Auckland ◽

J Kenneth Baillie ◽

Eleanor Barnes ◽

...

Keyword(s):

Symptom Onset ◽

Severe Disease ◽

Acute Infection ◽

Laboratory Diagnosis ◽

Rt Pcr ◽

Serum Samples ◽

Blood Samples ◽

Viral Loads ◽

Clinical Cohort ◽

Copy Numbers

ABSTRACTBackgroundLaboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood.MethodsWe undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=111 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples.ResultsWe identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/143 (0%, 95%CI 0.0-2.5%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA.ConclusionsvRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

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Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection

10.1101/2020.08.06.20169367 ◽

2020 ◽

Cited By ~ 16

Author(s):

Katharine HD Crawford ◽

Adam S Dingens ◽

Rachel Eguia ◽

Caitlin R Wolf ◽

Naomi Wilcox ◽

...

Keyword(s):

Symptom Onset ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Neutralizing Antibody ◽

Spike Protein ◽

Early Immune Response ◽

Antibody Titers ◽

Antibody Levels ◽

Time Frames ◽

Initial Peak

Most individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ≈30 and 152 days post-symptom onset from a prospective cohort of 34 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post-symptom onset. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

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