Viral dynamics and antibody responses in people with asymptomatic SARS-CoV-2 infection

AbstractOver 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming “herd-immunity” through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.

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Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19

10.21203/rs.3.rs-47021/v1 ◽

2020 ◽

Author(s):

Shidan Tosif ◽

Melanie Neeland ◽

Philip Sutton ◽

Paul Licciardi ◽

Sohinee Sarkar ◽

...

Keyword(s):

Immune Responses ◽

Chronic Exposure ◽

Family Members ◽

Asymptomatic Infection ◽

Antibody Responses ◽

Healthy Controls ◽

Serological Testing ◽

Igg Antibody ◽

Cytokine Responses ◽

Cellular Immune

Abstract Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have mild or asymptomatic infection, but the underlying immunological differences remain unclear. We describe clinical features, virology, longitudinal cellular and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who were repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children were similar to their parents at all timepoints. All family members had salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincided with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child had IgG antibody detected against the S1 protein and virus neutralising activity ranging from just detectable to robust titers. Using a systems serology approach, we show that all family members demonstrated higher levels of SARS-CoV-2-specific antibody features than healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological evidence of infection. This raises the possibility that despite chronic exposure, immunity in children prevents establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may therefore not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

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ADDRESSING THE ISSUE OF СOVID-19, SARS-COV-2 VIRUS AND THE DISEASE

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2020-99-6-15-31 ◽

2020 ◽

Vol 99 (6) ◽

pp. 15-31

Author(s):

A.A. Korenkova ◽

◽

E.M. Mayorova ◽

V.V. Bahmetjev ◽

M.V. Tretyak ◽

...

Keyword(s):

Public Health ◽

Immune Responses ◽

Molecular Mechanisms ◽

Herd Immunity ◽

Significant Problem ◽

Prevention Measures ◽

Optimal Therapy ◽

The World ◽

Public Health Challenge ◽

Coronavirus Infection

The new coronavirus infection has posed a major public health challenge around the world, but new data on the disease raises more questions than answers. The lack of optimal therapy is a significant problem. The article examines the molecular mechanisms of SARS-CoV-2 infection and the pathogenesis of COVID-19, special attention is paid to features of pathological processes and immune responses in children. COVID-19 leads to a wide diversity of negative outcomes, many of which can persist for at least months. Many of the consequences have yet to be identified. SARS-CoV-2 may provoke autoimmune reactions. Reinfection, herd immunity, vaccines and other prevention measures are also discussed in this review.

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Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

Infectious Agents and Cancer ◽

10.1186/s13027-021-00375-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ernesta Cavalcanti ◽

Maria Antonietta Isgrò ◽

Domenica Rea ◽

Lucia Di Capua ◽

Giusy Trillò ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Healthcare Workers ◽

Geometric Mean ◽

Vaccination Strategy ◽

Antibody Responses ◽

Cancer Center ◽

Serum Samples ◽

Humoral Immune ◽

History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice

Nature Communications ◽

10.1038/s41467-021-23173-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Alexandra J. Spencer ◽

Paul F. McKay ◽

Sandra Belij-Rammerstorfer ◽

Marta Ulaszewska ◽

Cameron D. Bissett ◽

...

Keyword(s):

Immune Response ◽

Clinical Trials ◽

T Cells ◽

Immune Responses ◽

Viral Vectors ◽

Cytotoxic T Cells ◽

Antibody Responses ◽

Limited Data ◽

Vectored Vaccine ◽

Cellular Immune

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

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Impact of the COVID-19 Vaccine on Asymptomatic Infection Among Patients Undergoing Pre-Procedural COVID-19 Molecular Screening

Clinical Infectious Diseases ◽

10.1093/cid/ciab229 ◽

2021 ◽

Cited By ~ 4

Author(s):

Aaron J Tande ◽

Benjamin D Pollock ◽

Nilay D Shah ◽

Gianrico Farrugia ◽

Abinash Virk ◽

...

Keyword(s):

United States ◽

Relative Risk ◽

Healthcare System ◽

The United States ◽

Asymptomatic Infection ◽

Screening Tests ◽

Molecular Screening ◽

Molecular Tests ◽

Asymptomatic Individuals ◽

The Impact

Abstract Background Several vaccines are now clinically available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. The impact of vaccines on asymptomatic SARS-CoV-2 infection is largely unknown. Methods We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39,156) within a large United States healthcare system who underwent 48,333 pre-procedural SARS-CoV-2 molecular screening tests between December 17, 2020 and February 8, 2021. The primary exposure of interest was vaccination with at least one dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received at least one dose of vaccine, as compared to persons who had not received vaccine during the same time period. Relative risk was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs. non-local), healthcare system regions, and repeated screenings among patients using mixed effects log-binomial regression. Results Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3,006 tests performed on vaccinated patients and 1,436 (3.2%) of 45,327 tests performed on unvaccinated patients (RR=0.44 95% CI: 0.33-0.60; p<.0001). Compared to unvaccinated patients, the risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after 1 st dose (RR=0.21; 95% CI: 0.12-0.37; p<.0001) and >0 days after 2 nd dose (RR=0.20; 95% CI: 0.09-0.44; p<.0001) in the adjusted analysis. Conclusions COVID-19 vaccination with an mRNA-based vaccine showed a significant association with a reduced risk of asymptomatic SARS-CoV-2 infection as measured during pre-procedural molecular screening. The results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.

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Pathogenicity of novel goose-origin astrovirus causing gout in goslings

BMC Veterinary Research ◽

10.1186/s12917-020-02739-z ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Dan Yin ◽

Jiajun Tian ◽

Jing Yang ◽

Yi Tang ◽

Youxiang Diao

Keyword(s):

Biochemical Parameters ◽

Clinical Symptoms ◽

Future Research ◽

Tissue Tropism ◽

Virus Shedding ◽

Viral Loads ◽

Blood Biochemical ◽

Copy Numbers ◽

Viral Copy ◽

Kidney Liver

Abstract Background A novel goose-origin astrovirus (GoAstV) has broken out across China in recent years, causing gout in goslings with a mortality rate of around 50%. However, our understanding of the dynamic distribution, tissue tropism and pathogenesis of GoAstV is incomplete. In order to assess its pathogenicity, one-day-old goslings were inoculated separately with GoAstV via oral and subcutaneous injection routes. Results Clinical symptoms, gross and microscopic lesions, blood biochemical parameters and viral loads were detected and recorded for 20 days after infection. Typical gout was observed in experimental goslings. GoAstV can be replicated in tissues and cause pathological damage, especially in the kidney, liver, heart and spleen. Virus-specific genomic RNA was detected in blood, cloacal swabs and all representative tissues, and virus shedding was detected up to 20 days after inoculation, suggesting that GoAstV has a wide tissue tropism and spread systematically after inoculation. The viral copy numbers examined in kidney were the highest, followed by spleen and liver. Conclusion This experiment determined the accurate value of viral loads and biochemical indicators of GoAstV-induced goslings. These findings increase our understanding of the pathogenicity of GoAstV in goslings and provide more reference for future research.

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Immune profiling reveals early disease trajectories associated with COVID-19 mortality: a sub-study from the ACTT-1 trial

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab035 ◽

2021 ◽

Author(s):

Joshua M Thiede ◽

Abigail R Gress ◽

Samuel D Libby ◽

Christine E Ronayne ◽

William E Matchett ◽

...

Keyword(s):

Immune Responses ◽

Antiviral Therapy ◽

Symptom Onset ◽

Antibody Responses ◽

Early Disease ◽

Host Immune Responses ◽

Study Enrollment ◽

Cytokine Responses ◽

Study Participants ◽

Immune Profiling

Abstract COVID-19 outcomes are linked to host immune responses and may be impacted by antiviral therapy. We investigated antibody and cytokine responses in ACTT-1 study participants enrolled at our center. We studied serum specimens from 19 hospitalized adults with COVID-19 randomized to treatment with remdesivir or placebo. We assessed SARS-CoV-2 antibody responses and identified cytokine signatures using hierarchical clustering. We identified no clear immunologic trends attributable to remdesivir treatment. Seven subjects were initially seronegative at study enrollment, and all four deaths occurred in this group with more recent symptom onset. We identified three dominant cytokine signatures, demonstrating different disease trajectories.

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A Novel Orthohepadnavirus Identified in a Dead Maxwell’s Duiker (Philantomba maxwellii) in Taï National Park, Côte d’Ivoire

Viruses ◽

10.3390/v11030279 ◽

2019 ◽

Vol 11 (3) ◽

pp. 279 ◽

Cited By ~ 1

Author(s):

Jan Gogarten ◽

Markus Ulrich ◽

Nishit Bhuva ◽

Joel Garcia ◽

Komal Jain ◽

...

Keyword(s):

Cote D'ivoire ◽

National Park ◽

Côte D’Ivoire ◽

New Technologies ◽

Cote D’Ivoire ◽

Taï National Park ◽

Côte D'ivoire ◽

Copy Numbers ◽

Viral Copy ◽

Tai National Park

New technologies enable viral discovery in a diversity of hosts, providing insights into viral evolution. We used one such approach, the virome capture sequencing for vertebrate viruses (VirCapSeq-VERT) platform, on 21 samples originating from six dead Maxwell’s duikers (Philantomba maxwellii) from Taï National Park, Côte d’Ivoire. We detected the presence of an orthohepadnavirus in one animal and characterized its 3128 bp genome. The highest viral copy numbers were detected in the spleen, followed by the lung, blood, and liver, with the lowest copy numbers in the kidney and heart; the virus was not detected in the jejunum. Viral copy numbers in the blood were in the range known from humans with active chronic infections leading to liver histolytic damage, suggesting this virus could be pathogenic in duikers, though many orthohepadnaviruses appear to be apathogenic in other hosts, precluding a formal test of this hypothesis. The virus was not detected in 29 other dead duiker samples from the Côte d’Ivoire and Central African Republic, suggesting either a spillover event or a low prevalence in these populations. Phylogenetic analysis placed the virus as a divergent member of the mammalian clade of orthohepadnaviruses, though its relationship to other orthohepadnaviruses remains uncertain. This represents the first orthohepadnavirus described in an artiodactyl. We have tentatively named this new member of the genus Orthohepadnavirus (family Hepadnaviridae), Taï Forest hepadnavirus. Further studies are needed to determine whether it, or some close relatives, are present in a broader range of artiodactyls, including livestock.

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Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

Journal of Experimental Medicine ◽

10.1084/jem.20170161 ◽

2017 ◽

Vol 214 (9) ◽

pp. 2563-2572 ◽

Cited By ~ 9

Author(s):

Spencer W. Stonier ◽

Andrew S. Herbert ◽

Ana I. Kuehne ◽

Ariel Sobarzo ◽

Polina Habibulin ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Ebola Virus ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Cd8 T Cell ◽

Marburg Virus ◽

Antibody Responses ◽

Cd4 T Cell ◽

Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

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