High rates of SARS-CoV-2 infection in pregnant Ugandan women and association with stunting in infancy (preprint)

Background: SARS-CoV-2 has been well studied in resource-rich areas but many questions remain about effects of infection in African populations, particularly in vulnerable groups such as pregnant women. Methods: We describe SARS-CoV-2 immunoglobulin (Ig) G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. Results: From December 2020 to February 2022, among 400 unvaccinated pregnant women, serologic assessments revealed that 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected either prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time. No participants experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infection (-1.54 versus -0.37 and -0.51, p=0.009). Conclusion: Pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with shorter stature in early infancy.

Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients (preprint)

ImportanceData on the humoral and cellular immune response to primary and booster SARS-CoV-2 vaccination in immunosuppressed patients is limited. ObjectiveTo determine humoral and cellular response to primary and booster vaccination in immunosuppressed patients and identify variables associated with poor response. DesignRetrospective observational cohort study. SettingLarge healthcare system in Northern California. ParticipantsThis study included patients fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) who underwent clinical testing for anti-SARS-SoV-2 S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon gamma release assay (IGRA) from January 1, 2021 through November 15, 2021. A cohort of 18 immunocompetent volunteer healthcare workers were included as reference. No participants had a prior diagnosis of SARS-CoV-2 infection. Exposure(s)Immunosuppressive diseases and therapies. Main Outcome(s) and Measure(s)Humoral and cellular SARS-CoV-2 vaccine response as measured by anti-S1 IgG and SARS-CoV-2 IGRA, respectively, after primary and booster vaccination. Results496 patients (54% female; median age 50 years) were included in this study. Among immunosuppressed patients after primary vaccination, 62% (261/419) had positive anti-S1 IgG and 71% (277/389) had positive IGRA. After booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Immunosuppressive factors associated with low rates of humoral response after primary vaccination included anti-CD20 monoclonal antibodies (P<.001), sphingosine 1-phsophate (S1P) receptor modulators (P<.001), mycophenolate (P=.002), and B cell lymphoma (P=.004); those associated with low rates of cellular response included S1P receptor modulators (P<.001) and mycophenolate (P<.001). Of patients who responded poorly to primary vaccination, 16% (4/25) with hematologic malignancy or primary immunodeficiency developed a significantly increased humoral response after the booster dose, while 52% (14/27) with solid malignancy, solid organ transplantation, or autoimmune disease developed an increased response (P=.009). Only 5% (2/42) of immunosuppressed patients developed a significantly increased cellular response following the booster dose. Conclusions and RelevanceCellular vaccine response rates were higher than humoral response rates in immunosuppressed individuals after primary vaccination, particularly among those undergoing B cell targeting therapies. However, humoral response can be increased with booster vaccination, even in patients on B cell targeting therapies.

Magnitude and breadth of neutralizing antibody responses elicited by SARS-CoV-2 infection or vaccination (preprint)

Multiple SARS-CoV-2 variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. While the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.529) spike appear to diminish the efficacy of pre-existing immunity. Using pseudoparticles expressing the spike of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in naturally infected and in mRNA-vaccinated individuals. We observed that while boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta and Omicron variants, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses while responses were relatively reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

Cell-Mediated and Humoral Immune Response to 2-Dose SARS-CoV2 mRNA vaccination in Immunocompromised patient population (preprint)

Characterization of cell-mediated and humoral immune responses to SARS-CoV2 mRNA vaccine has implications for protective immunity in immunocompromised patients. However, studies have demonstrated poor humoral response to SARS-CoV2 mRNA vaccine in immunocompromised patients and data on cellular immune response are currently lacking. Here we compared immune response after 2-dose vaccination in 100 immunocompromised patients (solid organ transplant recipients, hematologic malignancy, autoimmune condition, and primary immunodeficiency) and 16 immunocompetent healthy healthcare workers. We find that 100% (CI=80.6-100%) of immunocompetent individuals show positive cell-mediated and humoral immune response post vaccination while only 50% (CI=40.4-59.6%) of immunocompromised patients show humoral immune response and 69% (CI=59.4-77.2%) have a positive cell-mediated immune response. 21% of immunocompromised patients have no humoral immune response or cell-mediated immune response and thus are likely vulnerable to SARS-CoV2 infection. Monitoring of immune response in immunocompromised populations, particularly in high-risk immunocompromised patients (solid organ transplant recipients, patients with severe autoimmunity, and those [≥]50 years), with clinical IGRA and serological assay after vaccination may identify patients who may benefit from revaccination or prophylactic monoclonal antibody therapy to prevent COVID-19 in this patient population

mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition (preprint)

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.

Heterogeneous immunological recovery trajectories revealed in post-acute COVID-19 (preprint)

The immunological picture of how different patients recover from COVID-19, and how those recovery trajectories are influenced by infection severity, remain unclear. We investigated 140 COVID-19 patients from diagnosis to convalescence using clinical data, viral load assessments, and multi-omic analyses of blood plasma and circulating immune cells. Immune-phenotype dynamics resolved four recovery trajectories. One trajectory signals a return to pre-infection healthy baseline, while the other three are characterized by differing fractions of persistent cytotoxic and proliferative T cells, distinct B cell maturation processes, and memory-like innate immunity. We resolve a small panel of plasma proteins that, when measured at diagnosis, can predict patient survival and recovery-trajectory commitment. Our study offers novel insights into post-acute immunological outcomes of COVID-19 that likely influence long-term adverse sequelae.

SARS-COV-2 antibody prevalence in patients on dialysis in the US in January 2021 (preprint)

Background: To estimate seroprevalence of SARS-CoV-2 antibodies in the US, the country with largest absolute numbers of COVID19 cases and deaths in the world, we conducted a cross-sectional assessment from a sample of patients receiving dialysis in January 2021. Methods: We tested remainder plasma of 21,424 patients receiving dialysis through the third-largest US dialysis organization, with facilities located nationwide. We used the Siemens spike protein receptor binding domain total antibody assay to estimate crude SARS-CoV-2 seroprevalence, and then estimated seroprevalence for the US dialysis and adult population by standardizing by age, sex and region. We also compared January 2021 seroprevalence and case-detection rates to that from a similar subsample of patients receiving dialysis who had been tested in July 2020. Results: Patients in the sample were disproportionately from older age and minority race/ethnic groups. Seroprevalence of SARS-CoV-2 was 18.9% (95% CI: 18.3-19.5%) in the sample, 18.7% (18.1-19.2%) standardized to the US dialysis population, and 21.3% (20.3-22.3%) standardized to the US adult population (range 15.3-20.8% in the Northeast and South respectively). Younger age groups (18-44 years), and persons self-identifying as Hispanic or living in Hispanic neighborhoods, and persons living in the poorest neighborhoods were among the subgroups with the highest seroprevalence (25.9% (24.1-27.8%), 25.1% (23.6-26.4%), 24.8% (23.2-26.5%) respectively). Compared to data from July 2020, we observed diminished variability in seroprevalence by geographic region and urban-rural status. Estimated case detection rate increased from 14% to 23% in July 2020 to January 2021. Conclusions: A year after the first case of SARS-CoV-2 infection was detected in the US, fewer than one in four adults have evidence of SARS-CoV-2 antibodies. Vaccine roll out to majority minority neighborhoods and poorer neighborhoods will be critical to disrupting the spread of infection.

Persistent SARS-CoV-2 infection and increasing viral variants in children and young adults with impaired humoral immunity (preprint)

BackgroundThere is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses. MethodsWe describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape. FindingsWe found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape. InterpretationOur results highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered. FundingThe work was partially funded by The Saban Research Institute at Childrens Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology.

Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19 (preprint)

The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.

Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates (preprint)

The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor-binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.

Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues (preprint)

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells encoding humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults convergent clones often express mutated IgM or IgD in blood and are class-switched in lymphoid tissues; in contrast, children have abundant class-switched convergent clones in blood. Consistent with serological reports, pre-pandemic children had class-switched convergent clones to SARS-CoV-2, enriched in cross-reactive clones for seasonal coronaviruses, while adults showed few such clones in blood or lymphoid tissues. These results extend age-related and anatomical mapping of human humoral pathogen-specific immunity. One Sentence SummaryChildren have elevated frequencies of pathogen-specific class-switched memory B cells, including SARS-CoV-2-binding clones.

Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report. (preprint)

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Cyclooxgenase-2 is induced by SARS-CoV-2 infection but does not affect viral entry or replication (preprint)

Identifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 (COVID-19) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain and inflammation, could modulate both SARS-CoV-2 infection and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which mediate the production of prostaglandins (PGs). PGE2, one of the most abundant PGs, has diverse biological roles in homeostasis and inflammatory responses. Previous studies have shown that NSAID treatment or inhibition of PGE2 receptor signaling leads to upregulation of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2, thus raising concerns that NSAIDs could increase susceptibility to infection. COX/PGE2 signaling has also been shown to regulate the replication of many viruses, but it is not yet known whether it plays a role in SARS-CoV-2 replication. The purpose of this study was to dissect the effect of NSAIDs on COVID-19 in terms of SARS-CoV-2 entry and replication. We found that SARS-CoV-2 infection induced COX-2 upregulation in diverse human cell culture and mouse systems. However, suppression of COX-2/PGE2 signaling by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 expression, viral entry, or viral replication. Our findings suggest that COX-2 signaling driven by SARS-CoV-2 may instead play a role in regulating the lung inflammation and injury observed in COVID-19 patients.

Reanalysis of MERS, SARS and COVID-19 Infection Datasets using VirOmics Playground Reveals Common Patterns in Gene and Protein Expression (preprint)

Three lethal lower respiratory tract coronavirus epidemics have occurred over the past 20 years. This coincided with major developments in genome-wide gene and protein expression analysis, resulting in a wealth of datasets in the public domain. Seven such in vitro studies were selected for comparative bioinformatic analysis through the VirOmics Playground, a user-friendly visualisation and exploration platform we recently developed. Despite the heterogeneous nature of the data sets, several commonalities could be observed across studies and species. Differences, on the other hand, reflected not only variations between species, but also other experimental variables, such as cell lines used for the experiments, infection protocols and potential discrepancies between transcriptome and proteome data. The results presented here are available online and can be replicated through the VirOmics Playground.

SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells (preprint)

Since the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several somatic cells, little is known about the infection of SASRS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that SARS-CoV-2 pseudovirus and GX_P2V could infect lung progenitor and even anterior foregut endoderm cells causing these cells death, which differentiated from human embryonic stem cells (hESCs). The infection and replication of SARS-CoV-2 and GX_P2V were inhibited when treated with whey protein of breastmilk and Remdesivir, confirming that these two viruses could infect lung progenitor and even anterior foregut endoderm. Moreover, we found that SARS-CoV-2 pseudovirus could infect endoderm and ectoderm. We found that whey protein blocked SARS-CoV-2 infecting these cells. In line with the SARS-CoV-2 results, GX_P2V could also infected endoderm and ectoderm, and also was inhibited by Remdesivir treatment. Although expressing coronavirus related receptor such as ACE2 and TMPRSS2, mesoderm cells are not permissive for SARS-CoV-2 and GX_P2V infection, which needed further to study the mechanisms. Interestingly, we also found that hESCs, which also express ACE2 and TMPRSS2 markers, are permissive for GX_P2V but not SARS-CoV-2 pseudovirus infection and replication, indicating the widespread cell types for GX_P2V infection. Heparin treatment blocked efficiently viral infection. These results provided insight that these stem cells maybe provided a stable repository of coronavirus function or genome. The potential consequence of SARS-CoV-2 and animal coronavirus such as GX_P2V infection in hESCs, germ layer and induced progenitors should be closely monitored.

Sequence Analysis for SNP Detection and Phylogenetic Reconstruction of SARS-CoV-2 Isolated from Nigerian COVID-19 Cases (preprint)

Background: Coronaviruses are a group of viruses that belong to the Family Coronaviridae, Genus Betacoronavirus. In December 2019, a new coronavirus disease (COVID-19) characterized by severe respiratory symptoms was discovered. The causative pathogen was a novel coronavirus known as 2019-nCoV and later as SARS-CoV-2. Within two months of its discovery, COVID-19 became a pandemic causing widespread morbidity and mortality. Methodology: Whole genome sequence data of SARS-CoV-2 isolated from Nigerian COVID-19 cases were retrieved by downloading from GISAID database. A total of 18 sequences that satisfied quality assurance (length > 29700 nts and number of unknown bases denoted as N < 5%) were used for the study. Multiple sequence alignment (MSA) was done in MAFFT (Version 7.471) while SNP calling was implemented in DnaSP (Version 6.12.03) respectively and then visualized in Jalview (Version 2.11.1.0). Phylogenetic analysis was with MEGA X software. Results: Nigerian SARS-CoV-2 had 99.9% genomic similarity with four large conserved genomic regions. A total of 66 SNPs were identified out of which 31 were informative. Nucleotide diversity assessment gave Pi = 0.00048 and average SNP frequency of 2.22 SNPs per 1000 nts. Non-coding genomic regions particularly 5 UTR and 3 UTR had a SNP density of 3.77 and 35.4 respectively. The region with the highest SNP density was ORF10 with a frequency of 8.55 SNPs/1000 nts). Majority (72.2%) of viruses in Nigeria are of L lineage with preponderance of D614G mutation which accounted for 11 (61.1%) out of the 18 viral sequences. Nigeria SARS-CoV-2 revealed 3 major clades namely Oyo, Ekiti and Osun on a maximum likelihood phylogenetic tree. Conclusion and Recommendation: Nigerian SARS-CoV-2 reveals high mutation rate together with preponderance of L lineage and D614G mutants. Implication of these mutations for SARS-CoV-2 virulence and the need for more aggressive testing and treatment of COVID-19 in Nigeria is discussed. Additionally, attempt to produce testing kits for COVID-19 in Nigeria should consider the conserved regions identified in this study. Strict adherence to COVID-19 preventive measure is recommended in view of Nigerian SARS-CoV-2 phylogenetic clustering pattern, which suggests intensive community transmission possibly rooted in communal culture characteristic of many ethnicities in Nigeria.

Nitazoxanide and JIB-04 have broad-spectrum antiviral activity and inhibit SARS-CoV-2 replication in cell culture and coronavirus pathogenesis in a pig model (preprint)

Pathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Two compounds, nitazoxanide and JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50 of 4.90 M and 0.69 M, respectively, with specificity indices of greater than 150. Both inhibitors had in vitro antiviral activity in multiple cell types against some DNA and RNA viruses, including porcine transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved body weight gain and survival. These results highlight the potential utility of nitazoxanide and JIB-04 as antiviral agents against SARS-CoV-2 and other viral pathogens.

SARS-CoV-2 Antibody Responses Correlate with Resolution of RNAemia But Are Short-Lived in Patients with Mild Illness (preprint)

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, could offer protective immunity, and may affect clinical outcomes of COVID-19 patients. We analyzed 625 serial plasma samples from 40 hospitalized COVID-19 patients and 170 SARS-CoV-2-infected outpatients and asymptomatic individuals. Severely ill patients developed significantly higher SARS-CoV-2-specific antibody responses than outpatients and asymptomatic individuals. The development of plasma antibodies was correlated with decreases in viral RNAemia, consistent with potential humoral immune clearance of virus. Using a novel competition ELISA, we detected antibodies blocking RBD-ACE2 interactions in 68% of inpatients and 40% of outpatients tested. Cross-reactive antibodies recognizing SARS-CoV RBD were found almost exclusively in hospitalized patients. Outpatient and asymptomatic individuals' serological responses to SARS-CoV-2 decreased within 2 months, suggesting that humoral protection may be short-lived.

A lesson from COVID-19 on inaccessibility of web-based information for disabled populations worldwide (preprint)

Many government websites and mobile content are inaccessible for people with vision, hearing, and cognitive disabilities. The COVID-19 pandemic highlighted these disparities when health authority website information, critical in providing resources for curbing the spread of the virus, remained inaccessible for disabled populations. The Web Content Accessibility Guidelines provide comparatively universally accepted guidelines for website accessibility. We utilized these parameters to examine the number of countries with or without accessible health authority websites. The resulting data indicate a dearth of countries with websites accessible for persons with disabilities. Methods of information dissemination must take into consideration individuals with disabilities, particularly in times of global health crises.