Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals

Background: Easily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.gov NCT04405570). Methods: Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. Results: Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. Conclusions: Molnupiravir is the first oral, direct acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

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“…Plasma samples were collected to evaluate immune response and serology using antigen-capture enzyme-linked immunosorbent assays. [17][18][19]…”

Section: Clinical and Immunologic Outcomesmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted June 17 May 12];Available from: https://www.prnewswire.com/news-releases/phase-3-preventiontrial-showed-81-reduced-risk-of-symptomatic-sars-cov-2-infections-with-subcutaneousadministration-of-regen-cov-casirivimab-with-imdevimab-301266366.html All rights reserved. No reuse allowed without permission.…”

mentioning

confidence: 99%

Molnupiravir, an Oral Antiviral Treatment for COVID-19

Fischer

Eron

Holman³

et al. 2021

Preprint

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189

175

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“…Plasma samples were heat inactivated at 56°C for 30 minutes, then total Ig binding to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was measured using a previously described enzyme-linked immunosorbent (ELISA) assay [16,17]. Briefly, biotinylated recombinant antigen produced in mammalian cells consisting of SARS-2 Spike RBD is captured on a 96-well ELISA plate coated with streptavidin.…”

Section: Serologymentioning

confidence: 99%

“…The serum sample at 1:40 dilution is incubated with the RBD-captured wells, and bound antigen detected using HRP conjugated anti-goat total (IgG, IgM and IgA) antibody on a microplate reader. This in-house ELISA was previously evaluated on a large panel of well characterized samples and shown to have high sensitivity and specificity for detecting SARS-CoV-2 infection [16,17].…”

Section: Serologymentioning

confidence: 99%

High household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color

Cerami

Rapp

Lin

et al. 2021

Preprint

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Background Few prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color. Methods and Findings This is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05). Conclusions SARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance.

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“…Others have found no consistent IgG/IgA correlation for intensity of production [34]. Quantitation by most methods increase with the severity of infection [33,34,36,41,50,52,56,60,[70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87]. Severe disease may be associated with a delay of the humoral response [88].…”

Section: Immunogens and Humoral Immunitymentioning

confidence: 99%

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Cimolai¹

2021

CHI

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In the absence of effective antiviral chemotherapy and still in the context of emerging vaccines for severe acute respiratory syndrome-CoV-2 infections, passive immunotherapy remains a key treatment and possible prevention strategy. What might initially be conceived as a simplified donor-recipient process, the intricacies of donor plasma, IV immunoglobulins, and monoclonal antibody modality applications are becoming more apparent. Key targets of such treatment have largely focused on virus neutralization and the specific viral components of the attachment Spike protein and its constituents (e.g., receptor binding domain, N-terminal domain). The cumulative laboratory and clinical experience suggests that beneficial protective and treatment outcomes are possible. Both a dose-and a time-dependency emerge. Lesser understood are the concepts of bioavailability and distribution. Apart from direct antigen binding from protective immunoglobulins, antibody effector functions have potential roles in outcome. In attempting to mimic the natural but variable response to infection or vaccination, a strong functional polyclonal approach attracts the potential benefits of attacking antigen diversity, high antibody avidity, antibody persistence, and protection against escape viral mutation. The availability and ease of administration for any passive immunotherapy product must be considered in the current climate of need. There is never a perfect product, but yet there is considerable room for improving patient outcomes. Given the variability of human genetics, immunity, and disease, and given the nuances of the virus and its potential for change, passive immunotherapy can be developed that will be effective for some but not all patients. An understanding of such patient variability and limitations is just as important as the understanding of the direct interactions between immunotherapy and virus.

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Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals

Cited by 16 publications

References 43 publications

Molnupiravir, an Oral Antiviral Treatment for COVID-19

Molnupiravir, an Oral Antiviral Treatment for COVID-19

High household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color

Passive Immunity Should and Will Work for COVID-19 for Some Patients

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