Interim Safety and Immunogenicity of COVID-19 Omicron-BA.1 Variant-Containing Vaccine in Children (preprint)

ObjectivesWe report interim safety and immunogenicity results from a phase 3 study of omicron-BA.1 variant-containing (mRNA-1273.214) primary vaccination series (Part 1) and booster dose (Part 2) in children aged 6 months to 5 years (NCT05436834). MethodsIn Part 1, SARS-CoV-2 unvaccinated participants, including participants who received placebo in the KidCOVE study (NCT04796896), received 2 doses of mRNA-1273.214 (25-g omicron-BA.1 and ancestral Wuhan-Hu-1 mRNA 1:1 co-formulation) primary series. In Part 2, participants who previously completed the mRNA-1273 (25-{micro}g) primary series in KidCOVE received a mRNA-1273.214 (10-g) booster dose. Primary objectives were safety, reactogenicity, and immunogenicity, including prespecified immune response success criteria. ResultsAt the data cutoff (December 5, 2022), 179 participants had received [≥]1 dose of mRNA-1273.214 primary series (Part 1) and 539 participants had received a mRNA-1273.214 booster dose (Part 2). The safety profile of mRNA-1273.214 primary series and booster dose was consistent with that of the mRNA-1273 primary series in this same age group, with no new safety concerns identified and no vaccine-related serious adverse events observed. Compared with neutralizing antibody responses induced by the mRNA-1273 primary series, both the mRNA-1273.214 primary series and booster elicited responses that were superior against omicron-BA.1 and non-inferior against ancestral Wuhan-Hu-1(D614G). ConclusionsmRNA-1273.214 was immunogenic against BA.1 and D614G in children aged 6 months to 5 years, with a comparable safety profile to mRNA-1273, when given as a 2-dose primary series or as a booster dose after the mRNA-1273 primary series. Clinical Trial RegistryNCT05436834

Association between PM2.5 air pollution, temperature, and sunlight during different infectious stages with the case fatality of COVID-19 in the United Kingdom: a modeling study (preprint)

Although the relationship between the environmental factors such as weather conditions and air pollution and COVID-19 case fatality rate (CFR) has been found, the impacts of these factors to which infected cases are exposed at different infectious stages (e.g., virus exposure time, incubation period, and at or after symptom onset) are still unknown. Understanding this link can help reduce mortality rates. During the first wave of COVID-19 in the United Kingdom (UK), the CFR varied widely between and among the four countries of the UK, allowing such differential impacts to be assessed. We developed a generalized linear mixed-effect model combined with distributed lag nonlinear models to estimate the odds ratio of the weather factors (i.e., temperature, sunlight, relative humidity, and rainfall) and air pollution (i.e., ozone, NO2, SO2, CO, PM10 and PM2.5) using data between March 26, 2020 and May 12, 2020 in the UK. After retrospectively time adjusted CFR was estimated using back-projection technique, the stepwise model selection method was used to choose the best model based on Akaike information criteria (AIC) and the closeness between the predicted and observed values of CFR. We found that the low temperature (8-11∘ C), prolonged sunlight duration (11-13hours) and increased PM2.5 (11-18g/m3) after the incubation period posed a greater risk of death (measured by odds ratio (OR)) than the earlier infectious stages. The risk reached its maximum level when the low temperature occurred one day after (OR = 1.76; 95% CI: 1.10-2.81), prolonged sunlight duration 2-3 days after (OR = 1.50; 95% CI: 1.03-2.18) and increased PM2.5 at the onset of symptom (OR =1.72; 95% CI: 1.30-2.26). In contrast, prolonged sunlight duration showed a protective effect during the incubation period or earlier. After reopening, many COVID-19 cases will be identified after their symptoms appear. The findings highlight the importance of designing different preventive measures against severe illness or death considering the time before and after symptom onset.

Clinical predictors and RT-PCR profile of prolonged viral shedding in patients with SARS-CoV-2 Omicron variant in Shanghai: A retrospective observational study

Objective To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Materials and methods Hospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, “early clearance” and ≥15 days, “late clearance”). Results 4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance. Conclusion The number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.

Application of serum antibody detection in the identification of transmission chain of COVID-19

Objective: To explore the transmission chain of COVID-19 by serum antibody detection, and to provide scientific evidence for the prevention and control of the epidemic.

Trajectories of chemosensory and cognitive functions up to 1.5 years after acute COVID-19 (preprint)

There is an increasing recognition of neurological manifestations from SARS-CoV-2 infection. Quantifications of such manifestations and their long-term dynamics in the general infected population are of essence in understanding the health and socioeconomic burden of neurological complications of COVID-19. Through rigorous empirical testing of over 800 volunteers, we present here repeated cross-sectional and longitudinal data that depict the trajectories of chemosensory functions, cognitive performances and depressive symptoms up to 1.5 years after acute COVID-19 in discharged patients with respect to non-infected controls. Overall, deficits in smell, taste and chemesthesis slowly resolved within about a year of discharge. Concerningly, cognitive impairments –– independent of elevated depressive symptoms and evident even in those with nonsevere disease –– showed no sign of improvement over time. In people over 50 years, COVID-19 was associated with a substantially increased risk for mild cognitive impairment. Our findings urge for cognitive and emotional interventions targeting COVID-19 convalescents.

East Asian summer monsoon enhanced by COVID-19 (preprint)

Anthropogenic emissions decreased dramatically during the COVID-19 pandemic, but its possible effect on monsoon is unclear. Based on coupled models participating in the COVID Model Intercomparison Project (COVID-MIP), we show modeling evidence that the East Asian summer monsoon (EASM) is enhanced in terms of both precipitation and circulation, and the amplitude of the forced response reaches about 1/3 of the standard deviation for interannual variability. The response of EASM to COVID-19 is consistent with the response to the removal of all anthropogenic aerosols simulated by atmospheric component models, which confirms the dominant role of the fast response to reduced aerosols. The observational evidence, i.e., the anomalously strong EASM observed in 2020 and 2021, also supports the simulated enhancement of EASM. The essential mechanism for the enhanced EASM in response to COVID-19 is the enhanced zonal thermal contrast between Asian continent and the western North Pacific in the troposphere, particularly at the upper troposphere, due to the reduced aerosol concentration over Asian continent and the associated latent heating feedback. As the enhancement of EASM is a fast response to the reduction in aerosols, the effect of COVID-19 on EASM dampens soon after the rebound of emissions based on the models participating in COVID-MIP.

Tracking the Transmission Dynamics of COVID-19 with a Time-Varying Coefficient State-Space Model (preprint)

The spread of COVID-19 has been greatly impacted by regulatory policies and behavior patterns that vary across counties, states, and countries. Population-level dynamics of COVID-19 can generally be described using a set of ordinary differential equations, but these deterministic equations are insufficient for modeling the observed case rates, which can vary due to local testing and case reporting policies and non-homogeneous behavior among individuals. To assess the impact of population mobility on the spread of COVID-19, we have developed a novel Bayesian time-varying coefficient state-space model for infectious disease transmission. The foundation of this model is a time-varying coefficient compartment model to recapitulate the dynamics among susceptible, exposed, undetected infectious, detected infectious, undetected removed, detected non-infectious, detected recovered, and detected deceased individuals. The infectiousness and detection parameters are modeled to vary by time, and the infectiousness component in the model incorporates information on multiple sources of population mobility. Along with this compartment model, a multiplicative process model is introduced to allow for deviation from the deterministic dynamics. We apply this model to observed COVID-19 cases and deaths in several US states and Colorado counties. We find that population mobility measures are highly correlated with transmission rates and can explain complicated temporal variation in infectiousness in these regions. Additionally, the inferred connections between mobility and epidemiological parameters, varying across locations, have revealed the heterogeneous effects of different policies on the dynamics of COVID-19.

Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2 (preprint)

Background: COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed.Methods: We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays’ performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence.Results: Combined IgG+IgM sensitivities ranged from 33.9% to 94.6%, while combined specificities ranged from 92.6% to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG+IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG+IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 mg/mL), followed by a similar LOD of 1.5 mg/mL for CareHealth, Cellex, KHB, and Vivachek.Conclusion: We provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.

Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2 (preprint)

BackgroundCOVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed. MethodsWe evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence. ResultsCombined IgG+IgM sensitivities ranged from 33.9% to 94.6%, while combined specificities ranged from 92.6% to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG+IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG+IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 g/mL), followed by a similar LOD of 1.5 g/mL for CareHealth, Cellex, KHB, and Vivachek. ConclusionWe provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.

Structure-function investigation of a new VUI-202012/01 SARS-CoV-2 variant (preprint)

The SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus) has accumulated multiple mutations during its global circulation. Recently, a new strain of SARS-CoV-2 (VUI 202012/01) had been identified leading to sudden spike in COVID-19 cases in South-East England. The strain has accumulated 23 mutations which have been linked to its immune evasion and higher transmission capabilities. Here, we have highlighted structural-function impact of crucial mutations occurring in spike (S), ORF8 and nucleocapsid (N) protein of SARS-CoV-2. Some of these mutations might confer higher fitness to SARS-CoV-2. SummarySince initial outbreak of COVID-19 in Wuhan city of central China, its causative agent; SARS-CoV-2 virus has claimed more than 1.7 million lives out of 77 million populations and still counting. As a result of global research efforts involving public-private-partnerships, more than 0.2 million complete genome sequences have been made available through Global Initiative on Sharing All Influenza Data (GISAID). Similar to previously characterized coronaviruses (CoVs), the positive-sense single-stranded RNA SARS-CoV-2 genome codes for ORF1ab non-structural proteins (nsp(s)) followed by ten or more structural/nsps [1, 2]. The structural proteins include crucial spike (S), nucleocapsid (N), membrane (M), and envelope (E) proteins. The S protein mediates initial contacts with human hosts while the E and M proteins function in viral assembly and budding. In recent reports on evolution of SARS-CoV-2, three lineage defining non-synonymous mutations; namely D614G in S protein (Clade G), G251V in ORF3a (Clade V) and L84S in ORF 8 (Clade S) were observed [2-4]. The latest pioneering works by Plante et al and Hou et al have shown that compared to ancestral strain, the ubiquitous D614G variant (clade G) of SARS-CoV-2 exhibits efficient replication in upper respiratory tract epithelial cells and transmission, thereby conferring higher fitness [5, 6]. As per latest WHO reports on COVID-19, a new strain referred as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) had been identified as a part of virological and epidemiological analysis, due to sudden rise in COVID-19 detected cases in South-East England [7]. Preliminary reports from UK suggested higher transmissibility (increase by 40-70%) of this strain, escalating Ro (basic reproduction number) of virus to 1.5-1.7 [7, 8]. This apparent fast spreading variant inculcates 23 mutations; 13 non-synonymous, 6 synonymous and 4 amino acid deletions [7]. In the current scenario, where immunization programs have already commenced in nations highly affected by COVID-19, advent of this new strain variant has raised concerns worldwide on its possible role in disease severity and antibody responses. The mutations also could also have significant impact on diagnostic assays owing to S gene target failures.

Spike protein disulfide disruption as a potential treatment for SARS-CoV-2 (preprint)

The coronaviral pandemic is exerting a tremendously detrimental impact on global health, quality of life and the world economy, emphasizing the need for effective medications for current and future coronaviral outbreaks as a complementary approach to vaccines. The Spike protein, responsible for cell receptor binding and viral internalization, possesses multiple disulfide bonds raising the possibility that disulfide-reducing agents might disrupt Spike function, prevent viral entry and serve as effective drugs against SARS-CoV-2. Here we show the first experimental evidence that reagents capable of reducing disulfide bonds can inhibit viral infection in cell-based assays. Molecular dynamics simulations of the Spike receptor-binding domain (RBD) predict increased domain flexibility when the four disulfide bonds of the domain are reduced. This flexibility is particularly prominent for the surface loop, comprised of residues 456-490, which interacts with the Spike cell receptor ACE2. Consistent with this finding, the addition of exogenous disulfide bond reducing agents affects the RBD secondary structure, lowers its melting temperature from 52 to 36-39{degrees}C and decreases its binding affinity to ACE2 by two orders of magnitude at 37{degrees}C. Finally, the reducing agents dithiothreitol (DTT) and tris(2-carboxyethyl)phosphine (TCEP) inhibit viral replication at high {micro}M - low mM levels with a negligible effect on cell viability at these concentrations. The antiviral effect of monothiol-based reductants N-Acetyl-L-cysteine (NAC) and reduced glutathione (GSH) was not observed due to decreases in cell viability. Our research demonstrates the clear potential for medications that disrupt Spike disulfides as broad-spectrum anticoronaviral agents and as a first-line defense against current and future outbreaks.

The ancient cardioprotective mechanisms of ACE2 bestow SARS-CoV-2 with a wide host range (preprint)

SARS-CoV-2 infects a broader range of mammalian species than previously anticipated, suggesting there may be additional unknown hosts wherein the virus can evolve and potentially circumvent effective vaccines. We find that SARS-CoV-2 gains a wide host range by binding ACE2 sites essential for ACE2 carboxypeptidase activity. Six mutations found only in rodent species immune to SARS-CoV-2 are sufficient to abolish viral binding to human and dog ACE2. This is achieved through context-dependent mutational effects (intramolecular epistasis) conserved despite ACE2 sequence divergence between species. Across mammals, this epistasis generates sequence-function diversity, but through structures all bound by SARS-CoV-2. Mutational trajectories to the mouse conformation not bound by SARS-CoV-2 are blocked, by single mutations functionally deleterious in isolation, but compensatory in combination, explaining why human polymorphisms at these sites are virtually non-existent. Closed to humans, this path was opened to rodents via permissive cardiovascular phenotypes and ancient increases to ACE2 activity, serendipitously granting SARS-CoV-2 immunity. This reveals how ancient evolutionary trajectories are linked with unprecedented phenotypes such as COVID-19 and suggests extreme caution should be taken to monitor and prevent emerging animal reservoirs of SARS-CoV-2. One sentence summaryA conserved mechanism essential for ACE2 catalytic activity is exploited by SARS-CoV-2 binding, allowing the virus to infect a wide range of species.

SARS-CoV-2 Fusion Peptide has a Greater Membrane Perturbating Effect than SARS-CoV with Highly Specific Dependence on Ca2+ (preprint)

Coronaviruses are a major infectious disease threat, and include the zoonotic-origin human pathogens SARS-CoV-2, SARS-CoV, and MERS-CoV (SARS-2, SARS-1, and MERS). Entry of coronaviruses into host cells is mediated by the spike (S) protein. In our previous ESR studies, the local membrane ordering effect of the fusion peptide (FP) of various viral glycoproteins including the S of SARS-1 and MERS has been consistently observed. We previously determined that the sequence immediately downstream from the S2 cleavage site is the bona fide SARS-1 FP. In this study, we used sequence alignment to identify the SARS-2 FP, and studied its membrane ordering effect. Although there are only three residue difference, SARS-2 FP induces even greater membrane ordering than SARS-1 FP, possibly due to its greater hydrophobicity. This may be a reason that SARS-2 is better able to infect host cells. In addition, the membrane binding enthalpy for SARS-2 is greater. Both the membrane ordering of SARS-2 and SARS-1 FPs are dependent on Ca2+, but that of SARS-2 shows a greater response to the presence of Ca2+. Both FPs bind two Ca2+ ions as does SARS-1 FP, but the two Ca2+ binding sites of SARS-2 exhibit greater cooperativity. This Ca2+ dependence by the SARS-2 FP is very ion-specific. These results show that Ca2+ is an important regulator that interacts with the SARS-2 FP and thus plays a significant role in SARS-2 viral entry. This could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel.

Optimal test-assisted quarantine strategies for COVID-19 (preprint)

Background: Until herd immunity occurs for COVID-19, quarantine will remain a pillar for disease mitigation. A 14-day quarantine, although widely recommended for self-quarantine after potential infections and mandated by many government agencies can be physically and mentally stressful for those under quarantine and leads to lost productivity. Testing during quarantine is currently implemented by businesses and governments as a promising method to shorten the duration of quarantine. However, to our knowledge, no study has been performed to evaluate the performance of test-assisted quarantines and to identify the most effective choices of testing schedule. Methods: Based on statistical models for the transmissibility and viral loads of SARS-CoV-2 infections and sensitivity of various SARS-CoV-2 tests, we performed extensive simulations to evaluate the performance of quarantine strategies with one or more tests administered during quarantine. Sensitivity analyses were performed to evaluate the impact of model assumptions on the selection of optimal strategies. Findings: We found that SARS-CoV-2 testing can effectively reduce the length of quarantine without compromising safety. Whereas a single RT-PCR test performed before the end of quarantine can reduce the duration of quarantine to 10 days, two tests can further reduce the duration to 8-days and three tests with a highly sensitive RT-PCR test can justify a 6-day quarantine. More strategic testing schedules and one more day of quarantine are needed if tests are administrated with a less sensitive but more cost-effective antigen test. Interpretation: Testing during quarantine could substantially reduce the length of quarantine, reducing the physical and mental stress caused by long quarantines. With increasing capacity and lowered costs of SARS-CoV-2 tests, testing-assisted quarantines could be safer and more cost-effective than 14-day quarantines and warrant more widespread use.

Knowledge, Attitude, and Practice of Nurses Towards the Prevention and Control of COVID-19 (preprint)

Background: Coronavirus disease 2019(COVID-19) has been spreading globally, with severe impacts on health and economies. Nursing is an essential component of medical care, and nurses’ knowledge, attitude, and practice (KAP) about the prevention and control of the disease directly affects patient’s outcomes ,but there is little know about the nurses’ KAP during the COVID-19 epidemic.Methods: An anonymous survey was conducted using customized questionnaires designed by Sojump platform. 1323 nurses in Wuhan were the survey object for the KAP survey. The survey included 48 questions regarding the basic information of nurses and knowledge, attitude, and prevention measures for COVID-19. Results: A total of 1323 nurses in Wuhan were included in the survey, of whom women (95.7%) under 40 years old (94.6%) accounted for the majority. Nurses have a comprehensive knowledge of problems such as the COVID-19 susceptible population, isolation ward layout process, environmental cleaning and disinfection, hand hygiene measures, infectious disease case reporting processes, standard prevention measures, and personal protection level, with more than 60% accuracy. However, they have a general lack of knowledge about the route of transmission of COVID-19, the use of protective equipment, patient management, medical waste disposal, and occupational exposure emergency response, with less than 45% accuracy. There was a gap between the attitude and the practice of nurses (p <0.05). Moreover, the knowledge level of nurses has an impact on their attitude (OR 1.52, 95% CI 1.10-2.08, p = 0.008), and title (OR 1.48, 95% CI 1.01-2.15, p = 0.042), place of work (OR 1.59, 95% CI 1.36-1.85, p <0.001), and attitude (OR 1.93, 95% CI 1.52-2.46, p <0.001) had an impact on their practice.Conclusion: The nurses in Wuhan during the epidemic have insufficient knowledge about COVID-19 infection prevention and control, and there are gaps in attitude and practice, which further affect their attitude and practice. It is therefore necessary to strengthen relevant knowledge training on COVID-19 among nurses.

Rapid Detection of Anti-SARS-CoV-2 IgM and IgG Using a Selenium Nanoparticle-based Lateral Flow Immunoassay (preprint)

Background: Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is highly transmissible. Early and rapid testing is necessary to effectively prevent and control the outbreak. Detection of SARS-CoV-2 antibodies with lateral flow immunoassay can achieve this goal. Antibody detection is especially effective for the detection of asymptomatic infection.Methods: In this study, SARS-CoV-2 nucleoprotein was expressed by E. coli and purified by affinity chromatography. We used the highly stable and sensitive selenium nanoparticle as the labeling probe coupled with the SARS-CoV-2 nucleoprotein to prepare a new SARS-CoV-2 antibody (IgM and IgG) detection kit. The sensitivity and specificity of the kit were verified by plasma of COVID-19 patients and health persons. Separate detection of IgM and IgG, such as in this assay, was performed in order to reduce mutual interference and improve the accuracy of the test results.Results: The SARS-CoV-2 nucleoprotein was purified on a nickel column, and the final purity was greater than 90%. The sensitivity of the kit was 94.74% and the specificity was 95.12% by 41 negative plasma samples and 19 positive plasma samples detection.Conclusions: The assay kit does not require any special device for reading the results and the readout is a simple color change that can be evaluated with the naked eye. This kit is suitable for rapid and real-time detection of the SARS-CoV-2 antibody.