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Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan - implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2
Preprints and early-stage research may not have been peer reviewed yet.
Abstract
Background
It is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China.
Methods
We included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded.
Results
IgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients.
Conclusions
Very few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.
... In addition, antibody detection may provide a complementary perspective, along with RT-qPCR testing, in the diagnosis of COVID-19 (24,25). At this time, it has yet to be established whether there is a long-term immune response against SARS-CoV-2 (12) or protection against reinfection (17). ...
... As demonstrated in Table 3, there was no significant correlation between days of symptom onset to collection of serum and antibody index/ratio to suggest waning of antibodies during the time period tested. This information is in contrast to a study in Wuhan, China that found 10% of patients lost SARS-CoV-2 antibodies within weeks of infection (12), although different serology tests were used in this case. However, it has been previously shown that more severe disease produces a stronger antibody response, and thus our mild disease cohort may result in a lower sensitivity (26). ...
The ability to detect antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently under investigation with various performance characteristics and indications for use. In this article, we analyzed the ability of the Abbott SARS-CoV-2 immunoglobulin class G (IgG), EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) IgG, and EuroImmun SARS-CoV-2 ELISA immunoglobulin class A (IgA) kits to detect evidence of previous infection with SARS-CoV-2. We tested 49 known coronavirus disease-19 (COVID-19) patients and 111 prepandemic stored serology specimens. This resulted in a sensitivity of 95.9%, 100.0%, and 91.3% and a specificity of 98.2%, 98.2%, and 90.8% respectively, using manufacturer recommended cutoffs after inconclusive results (one for EuroImmun IgG and five for EuroImmun IgA) being excluded in the final statistical analyses. Cross-reactivity of hepatitis C virus seropositive specimens was observed resulting in false positives (p < 0.05). If a two-tiered algorithmic approach was applied, that is, testing with Abbott SARS-CoV-2 assay followed by EuroImmun SARS-CoV-2 IgG, 100% specificity and sensitivity could be obtained after six inconclusive results were excluded from data set before statistical analyses. Performance characteristics presented demonstrate the superior performance of IgG class antibodies for investigating previous infections. In addition, utilizing a second antibody test for supplementary testing may significantly enhance performance, particularly in lower prevalence settings.
... Contact-tracing studies show mixed evidences, with either reduced [11][12][13] or similar [14] infection rates in children compared to adults. Duration of antibody protection against the virus is unknown and some early findings have suggested that it might not persist long once the infection has been resolved [15,16]. ...
... However, it aligns with results recently reported on SARS-CoV-2 antibody decay during convalescence. A preprint study describes loss of IgM antibodies in 31.4% of 1,470 adult patients hospitalized with COVID-19, after a median time of 41 days since symptoms onset, as well as loss of IgG antibodies in more than 10% of them, after 21 days post-symptom onset [15]. Another study with 37 asymptomatic but SARS-CoV-2 positive patients of all ages and equal number with severe symptoms found that 40% of asymptomatic individuals had undetectable levels of antibodies two months after infection, compared to 13% of those symptomatic [16]. ...
Background
Susceptibility of children and adults to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and persistence of antibody response to the virus after infection resolution remain poorly understood, despite their significant public health implications.
Methods
A cross-sectional seroprevalence study with prospective recruitment of volunteer families that included at least one first-reported adult case positive by SARS-CoV-2 PCR and at least one child aged less than 15 years living in the same household under strict home confinement was conducted in the Health Region of metropolitan Barcelona (Spain) during the pandemic period April 28-June 3, 2020. All household members were tested at home by a rapid SARS-CoV-2 antibody assay in finger-prick obtained capillary blood.
Results
A total of 381 family households including 381 first-reported PCR-positive adult cases and 1,084 contacts (672 children, 412 adults) were enrolled. SARS-CoV-2 infection seroprevalence rates were 17.6% (118/672) in children and 18.7% (77/335) in adult contacts (p=0.64). Among first-reported cases, seropositivity rates varied from 84.0% in adults previously hospitalized and tested within 6 weeks since the first positive PCR result to 31.5% in those not hospitalized and tested after that lag time (p<0.001). Nearly all (99.9%) positive pediatric contacts were asymptomatic or had mild symptoms.
Conclusion
Children appear to have similar probability as adults to become infected by SARS-CoV-2 in quarantined family households but remain largely asymptomatic once infected. Adult antibody protection against SARS-CoV-2 seems to be weak at early convalescence and beyond 6 weeks post-infection confirmation, especially in cases that have experienced mild disease.
... The copyright holder for this preprint this version posted July 17, 2020. 1) is split into a number of age classes, the age-groups have different contact rates with other age-groups and the disease progresses differently for each age-group, making the model behaviour more realistic. Our age-stratified model consists of 9 age classes, i.e., [0-10), [10][11][12][13][14][15][16][17][18][19][20], [20][21][22][23][24][25][26][27][28][29][30], [30][31][32][33][34][35][36][37][38][39][40], [40][41][42][43][44][45][46][47][48][49][50], [50-60), [60-70), [70-80), [80-∞). The age-stratified deterministic implementation provides a good balance between added complexity and computational resources. ...
... The parameter ζ denotes the fraction of the recovered patients losing immunity and becoming susceptible to SARS-CoV-2 again. Liu et al. [22] found that after SARS-CoV-2 infection, it is unlikely that long-lasting protective antibodies are produced. It is thus deemed likely that re-susceptibility will play an important role in future modeling work. ...
As a response to a rapidly rising number of SARS-CoV-2 infections, the Belgian government imposed strict social contact restrictions on March 13th, 2020. After nearly two months, the curve was succesfully flattened and social restrictions were gradually released. Unfortunately, pharmaceutical interventions are not yet available so it is expected that preventing COVID-19 outbreaks will depend mostly on the successful implementation of non-pharmaceutical interventions, hence the need for well-informed models. In this study, we built a deterministic, continuous-time, age-stratified-SEIRD model with detailed hospital dynamics. Because the hospitalization data for Belgium have not been made public yet by the Belgian scientific institute of public health, we computed the hospitalization parameters based on data from 370 patients in two Ghent (Belgium) hospitals. The basic reproduction number during March 2020 was estimated as R0 = 2.83 and the model fits the hospitalization and ICU admission incidence under lockdown measures well. In spite of the release of social restrictions, hospitalizations have been steadily declining. We recomputed the basic reproduction number under lockdown release and found that it had to be as low as R0 = 0.73 to explain the endemic trend under the observed community mobility data. We further found that although the basic reproduction number in the population older than 70 years was smaller than one, this group compromises nearly half of the expected hospitalizations. This indicates that protection of the elderly may be the most efficient way to reduce strain on the public health care system in case of another SARS-CoV-2 outbreak.
... A seroepidemiological study that combined PCR testing with antibody testing in a German community found 15.5% infection rate, 5 times higher than the official PCR-only-based report of 3.1% for the same community 25 . Also using both PCR tests and IgG/IgM antibody tests for cohorts of healthcare workers, hospitalized patients and general workers in Wuhan, China, it was found that IgG prevalence was only 4.0% in healthcare providers and 4.6% in general workers 26 . While direct comparisons may not be completely warranted owing to our modest sample number of 66, the trend of lower infection rate among healthcare workers compared to others in these reports [24][25][26] suggests that the infection rate in the community where UCTH is situated may even be higher than the 26% we have found. ...
... Also using both PCR tests and IgG/IgM antibody tests for cohorts of healthcare workers, hospitalized patients and general workers in Wuhan, China, it was found that IgG prevalence was only 4.0% in healthcare providers and 4.6% in general workers 26 . While direct comparisons may not be completely warranted owing to our modest sample number of 66, the trend of lower infection rate among healthcare workers compared to others in these reports [24][25][26] suggests that the infection rate in the community where UCTH is situated may even be higher than the 26% we have found. Thus, in spite of the relatively low case fatality rate in Nigeria based on Nigeria's Center for Disease Control (NCDC) data 27 which is about 2%, our result indicates the urgent need for enhanced diagnostic testing, contact tracing, isolation of infected individuals and more drastic measures to contain the pandemic in the community. ...
The coronavirus disease 2019 (COVID-19) is now a pandemic with devastating social and economic consequences. The extent of the spread of COVID-19 within populations is uncertain since diagnostic tests have not been carried out on all eligible persons and doing such diagnostic tests on everyone is much less feasible in developing countries such as Nigeria. Tests for antibodies to SARS-CoV-2, the virus that causes COVID-19, are more affordable, readily available, and require minimal training than current diagnostic tests. Employing a seroepidemiological strategy, serological tests were conducted on 66 volunteering staff and patients at the University of Calabar Teaching Hospital (UCTH), a Federal Government owned tertiary healthcare facility, to determine the extent of exposure to SARS-CoV-2, from 17th to 25th June 2020. Using a COVID-19 IgG/IgM Rapid Test Cassette with emergency use authorization (EUA) from the Food and Drug Administration (FDA) of the United States, it was observed that of the 66 samples tested, 5 (7.6%) were both IgG and IgM positive and 17 (26%) were IgG positive. Moreover, for 44 of the 66 participants, simultaneous tests were carried out using a rapid test kit from a different manufacturer but without FDA-EUA and all the results completely matched with the FDA-EUA kit, except one case where the FDA-EUA kit showed positive for both IgG and IgM while the other kit was positive only for IgM. The 26% positive IgG indicates a high exposure rate for the hospital staff and patients and points to community transmission where the facility is situated. Hence, immediate activation of WHO guidelines for controlling community transmission is called for. These results can further serve as a pilot study to guide public health policies in response to COVID-19 pandemic in both the general population and in healthcare settings.
... In addition, genes involved in the origin and spread of novel mutations may further reduce the efficacy of current vaccines and therapies [2]. Epidemiological data on the survivors of SARS-CoV-2 infection have shown the lack of long-lasting protective antibodies against the virus; further research and alternative solutions are essential to diversify the potential prophylactic methods available [3][4][5]. ...
Background
The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its “Generally Regarded as Safe” status, its potential adjuvant properties, and its tolerogenicity to the host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is highly transmissible and pathogenic. This study aimed to determine the potential of Lactiplantibacillus plantarum expressing SARS-CoV-2 epitopes as a mucosal vaccine against SARS-CoV-2.
Results
In this study, the possible antigenic determinants of the spike (S1–1, S1–2, S1–3, and S1–4), membrane (ME1 and ME2), and envelope (E) proteins of SARS-CoV-2 were predicted, and recombinant L. plantarum strains surface-displaying these epitopes were constructed. Subsequently, the immune responses induced by these recombinant strains were compared in vitro and in vivo. Most surface-displayed epitopes induced pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α and interleukin (IL)-6] and anti-inflammatory cytokines (IL-10) in lipopolysaccharide-induced RAW 264.7, with the highest anti-inflammatory to pro-inflammatory cytokine ratio in the S1–1 and S1–2 groups, followed by that in the S1–3 group. When orally administered of recombinant L. plantarum expressing SARS-CoV-2 epitopes in mice, all epitopes most increased the expression of IL-4, along with induced levels of TNF-α, interferon-gamma, and IL-10, specifically in spike protein groups. Thus, the surface expression of epitopes from the spike S1 protein in L. plantarum showed potential immunoregulatory effects, suggesting its ability to potentially circumvent hyperinflammatory states relevant to monocyte/macrophage cell activation. At 35 days post immunization (dpi), serum IgG levels showed a marked increase in the S1–1, S1–2, and S1–3 groups. Fecal IgA levels increased significantly from 21 dpi in all the antigen groups, but the boosting effect after 35 dpi was explicitly observed in the S1–1, S1–2, and S1–3 groups. Thus, the oral administration of SARS-CoV-2 antigens into mice induced significant humoral and mucosal immune responses.
Conclusion
This study suggests that L. plantarum is a potential vector that can effectively deliver SARS-CoV-2 epitopes to intestinal mucosal sites and could serve as a novel approach for SARS-CoV-2 mucosal vaccine development.
... Antibodies prevalence in England fell from 6.0% to 4.4% over three months, study finds [24]. In Wuhan, IgG antibodies prevalence were 89.8% in COVID-19 patients, 4.0% in healthcare providers, 4.6% in general workers, and 1.0% in other patients [25]. 8.3% tested positive for IgG in an asymptomatic population in Sergipe, Brazil [26]. ...
Background: Monitoring of the immunological status linked with coronavirus disease 2019 (COVID-19) infection in Yemen is practically absent. Several studies vary in study design, populations under study, serologic tests used, timing of sample collection, and quality.
Objective: Therefore, our study aimed to present the validation of immunological method namely rapid test for detection of immunoglobulin G (IgG) of COVID-19 infection immune response development in the blood of healthy participants )asymptomatic) were living in the COVID-19 pandemic area and of the patients who have undergone COVID-19 infection.
Methodology: Rapid test was validated that included the sensitivity, specificity, precision and accuracy parameters and used for sampling in research analysis. Participated volunteers of this study were provided written consent. The study was designed in one time cross sectional COVID-19 antibodies survey after three months of COVID-19 pandemic and implemented in four groups (N:72): the first group COVID-19 was recovered patients (n:18) that admitted in isolation department , Center of Tropical Medicine and Infectious Diseases (CTMID), Al Thawara Public Hospital Authority, Hodeidah, Yemen, the second group was contacts of severe patients (n:18), the third group was mild and moderate cases (n:18) that were treated at home ,and the fourth group was asymptomatic cases (n:18)”. Data obtained were analyzed based on appropriate statistical tools.
Results: The results of rapid test validation showed that is sensitive (85.19%; CI: 72.88 to 93.38%), specific (83.33%;CI: 58.58 to 96.42%) , precise (93.88%; CI : 68.73 – 102.52%) and accurate (86.11%; CI : 84.72 to 92.12%) for detection of IgG of COVID-19 in Hodeidah, Yemen. In total, 49 of 72 participants were rapid test positive, giving a prevalence of COVID-19 of 68.05%. The COVID-19 IgG antibodies were detected in 18/18 cases (100%) of recovered severe patients (high prevalence); 17/18 cases (94.44%) of contacts (high prevalence). In addition, IgG were detected in 11/18 cases (61.11%) of mild and moderate patients (middle prevalence) and 3/18 cases (16.66%) of asymptomatic (low prevalence).
Conclusion: The study concluded that COVID-19 IgG antibodies become detectable after symptom onset of severe cases and their contacts (high prevalence) based on validated immunological method. On the other hand, the antibodies were developed in mild and moderate patients (middle prevalence). The IgG were developed in asymptomatic patients (low prevalence). However, additional data are needed before modifying public health recommendations based on serologic test results.
Keywords: COVID -19 Immunological IgG antibodies prevalence Hodeidah Yemen.
... Antibodies prevalence in England fell from 6.0% to 4.4% over three months, study finds [24]. In Wuhan, IgG antibodies prevalence were 89.8% in COVID-19 patients, 4.0% in healthcare providers, 4.6% in general workers, and 1.0% in other patients [25]. 8.3% tested positive for IgG in an asymptomatic population in Sergipe, Brazil [26]. ...
Background: Monitoring of the immunological status linked with coronavirus disease 2019 (COVID-19) infection in Yemen is practically absent. Several studies vary in study design, populations under study, serologic tests used, timing of sample collection, and quality.
Objective: Therefore, our study aimed to present the validation of immunological method namely rapid test for detection of immunoglobulin G (IgG) of COVID-19 infection immune response development in the blood of healthy participants )asymptomatic) were living in the COVID-19 pandemic area and of the patients who have undergone COVID-19 infection.
Methodology: Rapid test was validated that included the sensitivity, specificity, precision and accuracy parameters and used for sampling in research analysis. Participated volunteers of this study were provided written consent. The study was designed in one time cross sectional COVID-19 antibodies survey after three months of COVID-19 pandemic and implemented in four groups (N:72): the first group COVID-19 was recovered patients (n:18) that admitted in isolation department , Center of Tropical Medicine and Infectious Diseases (CTMID), Al Thawara Public Hospital Authority, Hodeidah, Yemen, the second group was contacts of severe patients (n:18), the third group was mild and moderate cases (n:18) that were treated at home ,and the fourth group was asymptomatic cases (n:18)”. Data obtained were analyzed based on appropriate statistical tools.
Results: The results of rapid test validation showed that is sensitive (85.19%; CI: 72.88 to 93.38%), specific (83.33%;CI: 58.58 to 96.42%) , precise (93.88%; CI : 68.73 – 102.52%) and accurate (86.11%; CI : 84.72 to 92.12%) for detection of IgG of COVID-19 in Hodeidah, Yemen. In total, 49 of 72 participants were rapid test positive, giving a prevalence of COVID-19 of 68.05%. The COVID-19 IgG antibodies were detected in 18/18 cases (100%) of recovered severe patients (high prevalence); 17/18 cases (94.44%) of contacts (high prevalence). In addition, IgG were detected in 11/18 cases (61.11%) of mild and moderate patients (middle prevalence) and 3/18 cases (16.66%) of asymptomatic (low prevalence).
Conclusion: The study concluded that COVID-19 IgG antibodies become detectable after symptom onset of severe cases and their contacts (high prevalence) based on validated immunological method. On the other hand, the antibodies were developed in mild and moderate patients (middle prevalence). The IgG were developed in asymptomatic patients (low prevalence). However, additional data are needed before modifying public health recommendations based on serologic test results.
Keywords: COVID -19 Immunological IgG antibodies prevalence Hodeidah Yemen.
... Furthermore, it is evident that previously infected individuals are becoming reinfected [4][5][6][7][8][9][10], suggesting: (1) a suboptimal immune response; (2) that some individuals are not mounting an immune response; (3) waning levels and decreased avidity [11][12][13] of antibodies post-infection-as previously seen for SARS-CoV-1 [14] and MERS-CoV [15]-or (4) that the immune response is not protective across all the SARS-CoV-2 strains that have emerged. Identifying immunoglobulins that correlate with protection from infection or re-infection and disease may assist us in understanding the mechanisms behind an optimal immune response; this may also shed additional light on the reasons behind varying disease prognoses. ...
The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here, we aim to shed light on the importance of antibody titres and epitope utilization in protection from re-infection. Health care workers are highly exposed to SARS-CoV-2 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titres against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N = 300) during the second wave of the pandemic were identified by assessing the IgG anti-N titres before and after the second wave. We assessed epitope coverage and antibody titres between the ‘single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p = 0.019) and IgA (p = 0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p = 0.004) and anti-S titres (p = 0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.
... As such, antibody data provide a long-lasting measure of SARS-CoV-2 exposure, enabling analyses of the recent epidemic. Indeed, many seroprevalence surveys for SARS-CoV-2 have been reported [3][4][5][6][7][8] , including our own communitybased antibody prevalence study REACT-2 (REal-time Assessment of Community Transmission-2) 9 . REACT-2 is a series of cross-sectional national surveys using home-based unsupervised self-administered lateral flow immunoassay (LFIA) tests for SARS-CoV-2 IgG among random population samples of 100,000-200,000 adults over 18 years in England, UK 9 . ...
Background
Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.
Methods
Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.
Results
Automated analysis showed substantial agreement with human experts (Cohen’s kappa 0.90–0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7–99.4%) and sensitivity (90.1–97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).
Conclusions
Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.
... However, reports suggest that in 2-4 months, the patients with moderate COVID-19 symptoms, showed a swift decrease in the level of spike-RBD-specific IgG titers, signifying that the humoral immunity induced by SARS-CoV-2 is not long-term [35,36]. A very similar observation was reported against the nucleocapsid protein of SARS-CoV-2 [37]. Furthermore, lower IgG titers were found to be associated with an elevated level of virus clearance compared to the high IgG titers [38]. ...
The transmission of SARS-CoV-2 has caused serious health crises globally. So far, 7 vaccines that are already being assessed in Phase IV clinical trials are, Comirnaty/ Pfizer; Spikevax/Moderna (m RNA vaccine); Vaxzevria or Covishield; Ad26.
COV2.S; Ad5-nCoV (adenoviral vector-based vaccine); CoronaVac and BBIBP-CorV (inactivated virus vaccine). Besides, there are about 280 vaccines that are undergoing preclinical and clinical trials including Sputnik-V, Covaxin or BBV152, and
NVX-CoV2373. These vaccines are being studied for their immunological responses and efficiency against COVID-19, and have been reported to demonstrate efective T and B cell responses. However, the long-lasting immunity of these vaccine regimens still needs to be investigated. An in-depth understanding of the vaccine efficacy and immune control mechanism is imperative for the rational purposing and implementation of the vaccines. Hence, in this review, we have comprehensively discussed the immune response induced in COVID-19 patients, as well as in the convalescent individuals to avoid reinfection. Moreover, we have also summarized the immunological responses and prophylactic efficacy of various COVID-19 vaccine regimens. In this context, this review can give insights into the development of efective vaccines against SARS-CoV-2 and its variants in the future.
Keywords: COVID-19; convalescent individuals; immune response; clinical trial; vaccine regimens
... In particular, we could choose a stochastic disease model such as Abrams et al. (2020). Assumptions on immunity after recovery might also need to be revised as relevant studies become available; for example Long et al. (2020); Liu et al. (2020a). ...
Decision making in the face of a disaster requires the consideration of several complex factors. In such cases, Bayesian multi-criteria decision analysis provides a framework for decision making. In this paper, we present how to construct a multi-attribute decision support system for choosing between countermeasure strategies, such as lockdowns, designed to mitigate the effects of COVID-19. Such an analysis can evaluate both the short term and long term efficacy of various candidate countermeasures. The expected utility scores of a countermeasure strategy capture the expected impact of the policies on health outcomes and other measures of population well-being. The broad methodologies we use here have been established for some time. However, this application has many novel elements to it: the pervasive uncertainty of the science; the necessary dynamic shifts between regimes within each candidate suite of countermeasures; and the fast moving stochastic development of the underlying threat all present new challenges to this domain. Our methodology is illustrated by demonstrating in a simplified example how the efficacy of various strategies can be formally compared through balancing impacts of countermeasures, not only on the short term (e.g. COVID-19 deaths) but the medium to long term effects on the population (e.g. increased poverty).
... Исследования, посвященные изучению особенностей гуморального иммунного ответа к SARS-СoV-2 в этой категории повышенного риска заражения, немногочисленны и противоречивы. Так, по оценкам исследователей из КНР, при обследовании 19 555 МР специфические IgG к SARS-CoV-2 сохранялись только у 4% [10]. Данные изучения напряженности иммунитета к вирусу SARS-CoV-2 среди МР одного из госпиталей в Милане (Италия) в первой половине апреля 2020 г. показали, что IgG-антитела были выявлены у 7,4% обследованных, а IgM -у 14,4% [15]. ...
Relevance. Since the beginning of the epidemic in China, there have been reports of nosocomial cases of SARSCoV-2 infection, including among medical workers. Studies of the intensity of humoral immune response to the SARSCoV-2 virus among medical workers who are much more likely to have professional contact with COVID-19 patients than are of particular importance. The aim is to study the seroprevalence and features of the humoral immune response to SARS-CoV-2 among medical workers. Materials and methods. The study included 61 medical workers from a multidisciplinary hospital in Kazan, which was redesigned to provide medical care to patients with new coronavirus infection, using the method of random sampling. The control group consisted of 60 non-medical workers. For the determination of IgG, a solid-phase ELISA was used. Statistical processing of the results was carried out using MS Excel software. The error of the relative value (M±m) was calculated, and the 95% confidence interval of the frequency of occurrence. To assess the significance of differences, the Student’s test (t-test) was used for independent samples. Results. The proportion of those seropositive to SARS-CoV-2 in the study group was 45.9%, compared with 21.7% in the control group. Among medical workers seropositive to the SARS-CoV-2 virus, the proportion of asymptomatic forms was 18.5%, mild forms — 53.6%, moderate forms and severe forms 25%. Two forms of the formation of a humoral immune response among seropositive ones were revealed: the first is characterized by the gradual elimination of specific IgG antibodies to SARSCoV-2 after 8 weeks from the onset of the first symptoms of COVID-19, the second form is an increase in specific IgG to SARS-CoV-2 and a higher value of the coefficient level of IgM positivity to SARS-CoV-2 after 8–10 weeks from the onset of the first symptoms. The group of seropositive, “raising antibodies”, prevailed over the group of individuals “eliminating antibodies”. Among seropositive medical workers, two forms of the formation of a humoral immune response were revealed: synchronous with the parallel elimination of IgG and IgM antibodies and a parallel increase in IgG and IgM. Conclusion. The study of the level of humoral immunity to COVID-19 in medical workers is important in terms of planning both anti-epidemic measures and predicting the effectiveness of the response to vaccination to SARS-CoV-2.
... Currently, ELISAs are being developed to detect and measure the presence of antibodies against SARS-CoV-2. Recent studies have evaluated varied combinations of IgG, IgA, and IgM antibodies against S, N, and RBD in patient serum 5,9,[14][15][16][17] . However, there is a need to continuously evaluate IgG, IgA, and IgM antibodies against S, N, and RBD within different patient populations to provide a better understanding of COVID-19 as well as to assess the duration and the extent of antibody responses to natural infection. ...
Serological assays intended for diagnosis, sero-epidemiologic assessment, and measurement of protective antibody titers upon infection or vaccination are essential for managing the SARS-CoV-2 pandemic. Serological assays measuring the antibody responses against SARS-CoV-2 antigens are readily available. However, some lack appropriate characteristics to accurately measure SARS-CoV-2 antibodies titers and neutralization. We developed an Enzyme-linked Immunosorbent Assay (ELISA) methods for measuring IgG, IgA, and IgM responses to SARS-CoV-2, Spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins. Performance characteristics of sensitivity and specificity have been defined. ELISA results show positive correlation with microneutralization and Plaque Reduction Neutralization assays with infectious SARS-CoV-2. Our ELISA was used to screen healthcare workers in Louisville, KY during the first wave of the local pandemic in the months of May and July 2020. We found a seropositive rate of approximately 1.4% and 2.3%, respectively. Our analyses demonstrate a broad immune response among individuals and suggest some non-RBD specific S IgG and IgA antibodies neutralize SARS-CoV-2.
... The COVID-19 pandemic made it urgent for scientific communities to address a critical question: does the human body develop long-term immunity to the virus? While some large-scale studies suggest that it does (e.g., Iyer et al., 2020;Wu et al., 2020), other large-scale studies show that the effects are limited (e.g., Liu, Wu, Tao, Zeng, & Zhou, 2020;Pollán et al., 2020). Curiously, it is the collection of single-case patients with reinfection (e.g., Tillett et al., 2020) that initially became more decisive in addressing this question. ...
An important aim of research on bilingualism is to understand how the brain adapts to the demands of using more than one language. In this paper, we argue that pursuing such an aim entails valuing our research as a discovery process that acts on variety. Prescriptions about sample size and methodology, rightly aimed at establishing a sound basis for generalization, should be understood as being in the service of science as a discovery process. We propose and illustrate by drawing from previous and contemporary examples within brain and cognitive sciences, that this necessitates exploring the neural bases of bilingual phenotypes: the adaptive variety induced through the interplay of biology and culture. We identify the conceptual and methodological prerequisites for such exploration and briefly allude to the publication practices that afford it as a community practice and to the risk of allowing methodological prescriptions, rather than discovery, to dominate the research endeavor. "We have to remember that what we observe is not nature in itself, but nature exposed to our method of questioning." Werner Heisenberg (1958)
... We assumed in our model that there is a long-lasting protective immunity following infection which is consistent with previous human coronavirus types [29,30,32]. However, a recent study suggested that people are unlikely to produce long-lasting protective antibodies against this virus [49]. If, indeed, a rapid waning is possible, this highlights the importance to protect the elderly in regions of high outbreaks. ...
Background
Applying heavy nationwide restrictions is a powerful method to curtail COVID-19 transmission but poses a significant humanitarian and economic crisis. Thus, it is essential to improve our understanding of COVID-19 transmission, and develop more focused and effective strategies. As human mobility drives transmission, data from cellphone devices can be utilized to achieve these goals.
Methods
We analyzed aggregated and anonymized mobility data from the cell phone devices of> 3 million users between February 1, 2020, to May 16, 2020 — in which several movement restrictions were applied and lifted in Israel. We integrated these mobility patterns into age-, risk- and region-structured transmission model. Calibrated to coronavirus incidence in 250 regions covering Israel, we evaluated the efficacy and effectiveness in decreasing morbidity and mortality of applying localized and temporal lockdowns (stay-at-home order).
Results
Poorer regions exhibited lower and slower compliance with the restrictions. Our transmission model further indicated that individuals from impoverished areas were associated with high transmission rates. Considering a horizon of 1–3 years, we found that to reduce COVID-19 mortality, school closure has an adverse effect, while interventions focusing on the elderly are the most efficient. We also found that applying localized and temporal lockdowns during regional outbreaks reduces the overall mortality and morbidity compared to nationwide lockdowns. These trends were consistent across vast ranges of epidemiological parameters, and potential seasonal forcing.
Conclusions
More resources should be devoted to helping impoverished regions. Utilizing cellphone data despite being anonymized and aggregated can help policymakers worldwide identify hotspots and apply designated strategies against future COVID-19 outbreaks.
... Understanding the acquisition of immunity against the infection remains a paradox. While certain studies provided evidence that individuals exposed to the virus can acquire immunity even without manifesting clinical symptoms, others have reported the absence of acquired immunity even after the post-infection recovery [29,42,44,54,95]. Thus, it remains inconclusive whether exposure to the virus may confer immunity, which in turn raises the possible threat of reinfection and recurrent outbreaks. ...
The COVID-19 pandemic has elicited a rapid response from the scientific community with significant advances in understanding the causative pathogen (SARS-CoV-2). Mechanisms of viral transmission and pathogenesis, as well as structural and genomic details, have been reported, which are essential in guiding containment, treatment, and vaccine development efforts. Here, we present a concise review of the recent research in these domains and an exhaustive analysis of the genomic origins of SARS-CoV-2. Particular emphasis has been placed on the pathology and disease progression of COVID-19 as documented by recent clinical studies, in addition to the characteristic immune responses involved therein. Furthermore, we explore the potential of nanomaterials and nanotechnology to develop diagnostic tools, drug delivery systems, and personal protective equipment design within the ongoing pandemic context. We present this as a ready resource for researchers to gain succinct, up-to-date insights on SARS-CoV-2.
... Uncertain validity of the available antibody tests, inconsistencies in sampling methods, small numbers and use of selected groups have made many studies difficult to interpret 11 . Different acceptability criteria may apply to community-based studies where population-wide results are required than for studies focused on individual risk [11][12][13][14] . While not generally approved for individual care, self-administered lateral flow immunoassay (LFIA) tests done at home provide a means for obtaining reliable community-wide prevalence estimates rapidly and at scale, at reasonable cost 15,16 , by adjusting the results for known test performance 17 . ...
England has experienced a large outbreak of SARS-CoV-2, disproportionately affecting people from disadvantaged and ethnic minority communities. It is unclear how much of this excess is due to differences in exposure associated with structural inequalities. Here, we report from the REal-time Assessment of Community Transmission-2 (REACT-2) national study of over 100,000 people. After adjusting for test characteristics and re-weighting to the population, overall antibody prevalence is 6.0% (95% CI: 5.8-6.1). An estimated 3.4 million people had developed antibodies to SARS-CoV-2 by mid-July 2020. Prevalence is two- to three-fold higher among health and care workers compared with non-essential workers, and in people of Black or South Asian than white ethnicity, while age- and sex-specific infection fatality ratios are similar across ethnicities. Our results indicate that higher hospitalisation and mortality from COVID-19 in minority ethnic groups may reflect higher rates of infection rather than differential experience of disease or care.
... Liu et al. [228] analyzed the prevalence of IgG and IgM from individuals who tested positive for SARS-CoV-2 both in serological and RT-PCR tests and from healthcare individuals without COVID-19 diagnosis in Wuhan, China. Although a significant number of healthcare individuals had been infected with this virus, SARS-CoV-2-specific IgG was detected only in a few of them. ...
Objectives: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a beemade product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords “propolis”, “virus”, “antiviral”, “antimicrobial” and “coronavirus”.
Key findings: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines.
Summary: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals’ immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.
... Numerous human SARS-CoV-2-neutralizing antibodies have been recently reported; however, their binding affinities and pseudoviral-and viral-neutralizing abilities have varied (25)(26)(27)(28)(29)(30)(38)(39)(40). Liu et al. highlighted the short-duration protective effect of human SARS-CoV-2-neutralizing antibodies and raised concerns about the efficacy of future SARS-CoV-2 vaccines (41). In contrast to human antibodies, camel anti-MERS-CoVneutralizing antibodies, which were shown to cross-react with SARS-CoV-2, persist several years after infection. ...
The development of prophylactic and therapeutic agents for coronavirus disease 2019 (COVID-19) is a current global health priority. Here, we investigated the presence of cross-neutralizing antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in dromedary camels that were Middle East respiratory syndrome (MERS)-CoV-seropositive but MERS-CoV-free. The tested 229 dromedaries had anti-MERS-CoV camel antibodies with variable cross-reactivity patterns against SARS-CoV-2 proteins, including the S trimer, M, N, and E proteins. Using SARS-CoV-2 competitive immunofluorescence immunoassays and pseudovirus neutralization assays, we found medium-to-high titers of cross-neutralizing antibodies against SARS-CoV-2 in these animals. Through linear B cell epitope mapping using phage immunoprecipitation sequencing and a SARS-CoV-2 peptide/proteome microarray, we identified a large repertoire of betacoronavirus cross-reactive antibody specificities in these dromedaries and demonstrated that the SARS-CoV-2-specific VHH antibody repertoire is qualitatively diverse. This analysis revealed not only several SARS-CoV-2 epitopes that are highly immunogenic in humans, including a neutralizing epitope, but also epitopes exclusively targeted by camel antibodies. The identified SARS-CoV-2 cross-neutralizing camel antibodies are not proposed as a potential treatment for COVID-19. Rather, their presence in non-immunized camels supports the development of SARS-CoV-2 hyperimmune camels, which could be a prominent source of therapeutic agents for the prevention and treatment of COVID-19.
... In contrast with SARS, in which immunogenicity lasted for at least one year, preliminary data suggest that immunogenicity to COVID-19 may be lost as rapidly as a few weeks after symptom onset. [13][14][15] Lastly, infected individuals may not yet have seroconverted to produce IgG Ab. A recent study documented IgG seroconversion rates of 79.8% at 15 days after disease onset, suggesting that this is not the cause of the low serology rate. ...
Background
Although first responders (FRs) represent a high-risk group for exposure, little information is available regarding their risk of coronavirus disease 2019 (COVID-19) infection. The purpose of the current study was to determine the serological prevalence of past COVID-19 infection in a cohort of municipal law enforcement (LE) and firefighters (FFs).
Methods
Descriptive analysis of a de-identified data reporting Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) immunoglobulin G (IgG), or COR2G, serology results for municipal FRs. As part of the serology process, FRs were surveyed for COVID-19-like symptoms since February 2020 and asked to report any prior COVID-19 nasal swab testing. Descriptive statistics and two-sided Chi Square tests with Yates correction were used to compare groups.
Results
Of 318 FRs, 225 (80.2%) underwent serology testing (LE: 163/207 [78.7%]; FF: 92/111 [82.9%]). The prevalence of positive serology for all FRs tested was 3/255 (1.2%). Two LE (1.2%) and one FF (1.1%) had positive serology (P = 1.0). Two hundred and twenty-four FRs responded to a survey regarding prior symptoms and testing. Fifty-eight (25.9%) FRs (44 LE; 14 FFs) reported the presence of COVID-19-like symptoms. Of these, only nine (15.5%) received reverse transcriptase – polymerase chain reaction (RT-PCR) testing; none were positive. Two of the three FRs with positive serology reported no COVID-19-like symptoms and none of these responders had received prior nasal RT-PCR swabs. The overall community positive RT-PCR rate was 0.36%, representing a three-fold higher rate of positive seroprevalence amongst FRs compared with the general population (P = .07).
Conclusions
Amongst a cohort of municipal FRs with low community COVID-19 prevalence, the seroprevalence of SARS-CoV-19 IgG Ab was three-fold greater than the general community. Two-thirds of positive FRs reported a lack of symptoms. Only 15.5% of FRs with COVID-19-like symptoms received RT-PCR testing. In addition to workplace control measures, increased testing availability to FRs is critical in limiting infection spread and ensuring response capability.
... Delays in development or vanishing of antibodies can bias the IFR estimate upward by downward biased prevalence count. In Ref. [72] it was concluded that after SARS-CoV-2 infection, long-lasting protective antibodies are not likely produced. This is currently an open question in precision terms. ...
A bstract
The determination of the infection fatality rate (IFR) for the novel SARS-CoV-2 coronavirus is a key aim for many of the field studies that are currently being undertaken in response to the pandemic. The IFR together with the basic reproduction number R 0 , are the main epidemic parameters describing severity and transmissibility of the virus, respectively. The IFR can be also used as a basis for estimating and monitoring the number of infected individuals in a population, which may be subsequently used to inform policy decisions relating to public health interventions and lockdown strategies. The interpretation of IFR measurements requires the calculation of confidence intervals. We present a number of statistical methods that are relevant in this context and develop an inverse problem formulation to determine correction factors to mitigate time-dependent effects that can lead to biased IFR estimates. We also review a number of methods to combine IFR estimates from multiple independent studies, provide example calculations throughout this note and conclude with a summary and “best practice” recommendations. The developed code is available online.
... In some situations, the use of serological testing may also be applied to determine the immunity status of asymptomatic subjects with an epidemiological history of a high risk of exposure to people with COVID-19 (Lou et al., 2020). In such settings, serologic testing at appropriate intervals following contact with infected subjects might result in relatively fewer false-positive results (Liu et al., 2020b). ...
The COVID-19 pandemic has caused an unprecedented public health, social, and economic crisis. Improving understanding on available tests for detecting COVID-19 is critical for effective management of the pandemic. We proposed that a multidisciplinary expert panel can establish recommendations on ideal use of diagnostic tools, with a focus on RT-PCR and serological high-affinity antibodies (both IgM and IgG) tests for the Latin America region.
Study design
A collaborative multidisciplinary panel of 5 recognized experts in Latin America (an infectious disease specialist, three pathologists and an immunologist) was convened and supported by Roche Diagnostics to develop standard guidelines and an evidence-based document of best practices on the use of diagnostic tools for COVID-19.
Results
The authors reached consensus on the applicability of diagnostic tools to provide testing algorithms for the use of RT-PCR and serological high-affinity antibodies (both IgM and IgG) tests in three settings: 1) For asymptomatic subjects exposed to a SARS-CoV-2 infected person; 2) For epidemiological purposes and; 3) For symptomatic subjects.
Conclusion
The serological high-affinity SARS-Cov-2 antibodies (both IgM and IgG) tests play a key role in COVID-19 diagnosis. These tests can be applied for suspected false-negative RT-PCR results and for individual determination of response. The use of these tests can also contribute greatly to public health strategies, such as population screening and supporting vaccination planning. Serological status for high-affinity antibodies (both IgM and IgG) should be performed ideally 21 days after potential infectious contact, given that the majority of exposed individuals will have seroconverted.
... This agrees with findings by others. For example, Wu et al have shown that a small but significant number of patients recovered from COVID-19 lack SARS-CoV-2-neutralizing antibodies [63], and that Liu et al have found similar mortality risks between those COVID-19 patients who tested positive for IgG antibodies against SARS-CoV-2 and those who lacked antibodies against SARS-CoV-2 [64]. Therefore, those recovered patients with XLA, ARA, or CVID must have an activated T-cell immunity against SARS-CoV-2 virus. ...
In the ongoing COVID-19 pandemic, all COVID-19 patients are naïve patients as it is the first-time humans have been exposed to the SARS-CoV-2 virus. As with exposure to many viruses, individuals with pre-existing, compromised immune systems may be at increased risk of developing severe symptoms and/or dying because of (SARS-CoV-2) infection. To learn more about such individuals, we conducted a search and review of published reports on the clinical characteristics and outcomes of COVID-19 patients with pre-existing, compromised immune systems. Here we present our review of patients who possess pre-existing primary antibody deficiency (PAD) and those who are organ transplant recipients on maintenance immunosuppressants. Our review indicates different clinical outcomes for the patients with pre-existing PAD, depending on the underlying causes. For organ transplant recipients, drug-induced immune suppression alone does not appear to enhance COVID-19 mortality risk - rather, advanced age, comorbidities, and the development of secondary complications appears required.
... 16,17 Similar results have been reported with antibody responses specific to SARS-CoV-2 nucleocapsid protein. 18 A prospective study of 67 patients with COVID-19 who had high titres (peak titre >2 fold the cutoff value for a positive result) of nucleocapsid-specific IgM (up to 1:800) and IgG (up to 1:60) after symptom onset found that antibody titres were significantly higher in patients with severe disease than they were in patients without severe disease and were associated with clinical outcomes. 19 Furthermore, patients with COVID-19 and low IgG titres (ie, peak titre 1-2 fold the cutoff value for a positive result) had a higher rate of viral clearance than did patients with COVID-19 and high IgG titres (ie, strong antibody responders), again suggesting that strong antibody responses might be associated with more severe disease, and low antibody responses might be associated with higher rates of viral clearance. ...
Understanding immune responses to severe acute respiratory syndrome coronavirus 2 is crucial to understanding disease pathogenesis and the usefulness of bridge therapies, such as hyperimmune globulin and convalescent human plasma, and to developing vaccines, antivirals, and monoclonal antibodies. A mere 11 months ago, the canvas we call COVID-19 was blank. Scientists around the world have worked collaboratively to fill in this blank canvas. In this Review, we discuss what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 and relate this knowledge to the COVID-19 vaccines currently in phase 3 clinical trials.
... Also, the unexpected finding of lower rates of serologic conversion in our HCWs suggests the possibility that innate immunity may be greater among the HCWs, a hypothesis warranting further studies. Finally, the fact that all of our sero-positive HCWs have maintained antibody positivity for at least 8 weeks, with no reported re-infection, is encouraging, given the earlier reports of antibody evanescence [33,34]. ...
Understanding SARS-CoV-2 antibody prevalence as a marker of prior infection in a spectrum of healthcare workers ( HCWs ) may guide risk stratification and enactment of better health policies and procedures.
The present study reported on cross-sectional study to determine the prevalence and longevity of SARS-CoV-2 antibodies in HCWs at a regional hospital system in Orange County, California, between May and August, 2020.
Data from HCWs (n=3,458) were included in the analysis. Data from first responders (n=226) were also analyzed for comparison. A blood sample was collected at study enrollment and 8-week follow-up. Information on job duties, location, COVID-19 symptoms, polymerase chain reaction test history, travel since January 2020, and household contacts with COVID-19 was collected. Comparisons to estimated community prevalence were also evaluated.
Observed antibody prevalence was 0.93% and 2.58% at initial and 8-week follow-up, respectively, for HCWs, and 5.31% and 4.35% for first responders. For HCWs, significant differences ( p < .05) between negative vs. positive at initial assessment were found for age, race, fever, and loss of smell, and at 8-week follow-up for age, race, and all symptoms. Antibody positivity persisted at least 8 weeks in this cohort. Among 75 HCWs with self-reported prior PCR-confirmed COVID-19, 35 (46.7%) were antibody negative. Significant differences between negative vs. positive were observed in age and frequency of symptoms.
This study found considerably lower SARS-CoV-2 antibody prevalence among HCWs compared with prior published studies. This may be explained by better safety measures in the workplace, heightened awareness inside and outside of the workplace, possibly lower susceptibility due to innate immunity and other biological heterogeneity, and low COVID-19 prevalence in the community itself. HCWs with initial positive results had persistent positive serologies at 8 weeks. Further research is warranted to investigate factors influencing such lower prevalence in our HCWs.
... Furthermore, it is not yet known whether a person can get infected multiple times [18,19]. Preliminary studies suggest antibodies may last only a few weeks or months [20,21]. If one can get infected more than once, then the severity of the problem would be magnified. ...
Electrical energy is a vital part of modern life, and expectations for grid resilience to allow a continuous and reliable energy supply has tremendously increased even during adverse events (e.g., Ukraine cyber-attack, Hurricane Maria). The global pandemic COVID-19 has raised the electric energy reliability risk due to potential workforce disruptions, supply chain interruptions, and increased possible cybersecurity threats. The pandemic introduces a significant degree of uncertainly to the grid operation in the presence of other extreme events like natural disasters, unprecedented outages, aging power grids, high proliferation of distributed generation, and cyber-attacks. This situation increases the need for measures for the resiliency of power grids to mitigate the impacts of the pandemic as well as simultaneous extreme events. Solutions to manage such an adverse scenario will be multi-fold: a) emergency planning and organizational support, b) following safety protocol, c) utilizing enhanced automation and sensing for situational awareness, and d) integration of advanced technologies and data points for ML-driven enhanced decision support. Enhanced digitalization and automation resulted in better network visibility at various levels, including generation, transmission, and distribution. These data or information can be utilized to take advantage of advanced machine learning techniques for automation and increased power grid resilience. In this paper, a) we review the impact of COVID-19 on power grid operations and actions taken by operators/organizations to minimize the impact of COVID-19, and b) we have presented the recently developed tool and concepts using natural language processing (NLP) in the domain of machine learning and artificial intelligence that can be used for increasing resiliency of power systems in normal and in extreme scenarios such as COVID-19 pandemics.
... Antibody serosurveillance is an essential tool for monitoring the COVID-19 pandemic, offering a more comprehensive picture of who has been infected than swab testing of symptomatic individuals alone. In recent months, several countries have done largescale seroprevalence surveys, including the USA, 1,2 China, 3 Brazil, 4 England, 5 and Spain. 6 These studies have confirmed that the world is still in the early stages of the COVID-19 pandemic, with the majority of the populations surveyed testing negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. ...
... Interestingly, this excess mortality in males was identical when considering suspected and confirmed cases of COVID-19 deaths in care homes (results not shown), suggesting that most suspected cases were correctly diagnosed. This is also supported by the very good quantitative correspondence between the daily deaths attributed to COVID-19 (including suspected cases) and the daily deaths excess occurring in spring 2020 compared to previous years (Molenberghs et al. 2020;Wu et al. 2020). Despite their higher vulnerability, males constituted only 45.1% of COVID-19 deaths in Wallonia, a paradox resulting from the much lower proportion of males (3.9%) than females (9.2%) ≥65 years old living in care homes, while the care homes population has been more infected. ...
COVID-19 became pandemic in 2020 and causes higher mortality in males (M) than females (F) and among older people. In some countries, like Belgium, more than half of COVID-19 confirmed or suspected deaths occurring in spring 2020 concerned residents of care homes. The high incidence in this population is certainly linked to its peculiar age structure but could also result from its poorer general health condition and/or from a higher contamination through the staff of care homes, while protection equipment and testing capacity were initially limited. To address these issues, we used data from Wallonia (Belgium) to characterize the distribution of death rates among care home institutions, to compare the dynamics of deaths in and outside care homes, and to analyse how age and sex affected COVID-19 death rates inside and outside care homes. We also used annual death rates as a proxy for the health condition of each population. We found that: (1) COVID-19 death rate per institution varied widely from 0‰ to 340‰ (mean 43‰) and increased both with the size of the institution (number of beds) and with the importance of medical care provided. (2) 65% of COVID-19 deaths in Wallonia concerned residents of care homes where the outbreak started after but at a faster pace than the outbreak seen in the external population. (3) The impact of age on both annual and COVID-19 mortality closely follows exponential laws (i.e. Gompertz law) but mortality was much higher for the population living in care homes where the age effect was lower (mortality rate doubling every 20 years of age increment in care homes, 6 years outside them). (4) Both within and outside care homes, the ratio of M/F death rates was 1.6 for annual mortality but reached 2.0 for COVID-19 mortality, a ratio consistent among both confirmed and suspected COVID-19 deaths. (5) When reported to the annual death rate per sex and age, the COVID-19 relative mortality was little affected by age and reached 24% (M) and 18% (F) of their respective annual rate in nursing homes, while these percentages reduced to 10% (M) and 9% (F) in homes for elderly people (with less medical assistance), and to 5% (M) and 4% (F) outside of care homes. In conclusion, a c. 130x higher COVID-19 mortality rate found in care homes compared to the outside population can be attributed to the near multiplicative combination of: (1) a 11x higher mortality due to the old age of its residents, (2) a 3.8x higher mortality due to the low average health condition of its residents, and (3) probably a 3.5x higher infection rate (1.6x in homes for elderly people) due to the transmission by its staff, a problem more acute in large institutions. Our results highlight that nursing home residents should be treated as a very specific population, both for epidemiological studies and to take preventive measures, due to their extreme vulnerability to COVID-19.
... "Serosurvey" efforts, aimed at determining overall exposure and seroconversion rates in a population, provide a tool to identify exposure associated risk factors and can guide the rational utilization in a health care setting of personal protective equipment (PPE), in addition to return to work policies and providing psychological support to health care workers who are at risk of secondary mental health issues due to overwork and fear of contagion 8 . Although serological studies have been extensively used to determine local epidemic dynamics and population infection fatality rates, significant gaps persist in the current understanding of the humoral responses to SARS-CoV-2 in individuals with asymptomatic infections, with recent evidence suggesting that asymptomatic individuals may have a weaker humoral immune response to SARS-CoV-2 infection and an early reduction in antibody levels [9][10][11][12][13] . ...
Frontline healthcare workers (HCW) are a high-risk population for SARS-CoV-2 infection. Here we present results from a large serosurveillance study of 10,019 asymptomatic HCW conducted during April-May 2020, in eight hospital medical centers across the state of Oregon, USA during the initial peak of the pandemic. Free and voluntary testing was performed at 14 +/- 3 day intervals, over a 4-week window at each site, utilizing a lab-developed ELISA based on the Epitope Diagnostics COVID-19 nucleocapsid IgG detection Kit. We identified 253 SARS-CoV-2 IgG seropositive individuals among 10,019 total participants, representing a cross-sectional seroprevalence of 2.53%. Subgroup analysis identified differential seropositivity by job role, ranging from 8.03% among housekeepers, odds ratio 3.17 (95% CI 1.59-5.71), to 0.00% among anesthesiologists, odds ratio 0.00 (95% CI 0-0.26), both of which were significant. Over the course of the study, 17 seroconversions (0.25%) and 101 seroreversions (1.50%) were identified. Self-reported SARS-CoV-2 swab qPCR testing, when compared with subsequent serology on study, showed only modest agreement, κ = 0.47 (95% CI 0.32-0.62). Overall, these findings demonstrate relatively low seroprevalence and very low seroconversion rates among HCW in Oregon, USA, over a period in which aggressive social distancing measures were in place. The high rate of seroreversion observed in this cohort, and the relatively high discordance between SARS-CoV-2 serology and swab qPCR, highlight limitations of current detection methods, and stress the need for development of novel assessment methodologies to more accurately identify exposure (and/or immunity) to SARS-CoV-2 in this population.
... These insights suggest a strategy for controlling diseases which do not to confer immunity and may apply to SARS-CoV-2, as recent studies indicate that the disease might not confer immunity [58][59][60] . More generally, this strategy may be applied in the context of new diseases, for which it is unknown and unknowable whether contracting and recovering from the disease grants immunity 61 . ...
In numerous contexts, individuals may decide whether they take actions to mitigate the spread of disease, or not. Mitigating the spread of disease requires an individual to change their routine behaviours to benefit others, resulting in a ‘disease dilemma’ similar to the seminal prisoner’s dilemma. In the classical prisoner’s dilemma, evolutionary game dynamics predict that all individuals evolve to ‘defect.’ We have discovered that when the rate of cooperation within a population is directly linked to the rate of spread of the disease, cooperation evolves under certain conditions. For diseases which do not confer immunity to recovered individuals, if the time scale at which individuals receive accurate information regarding the disease is sufficiently rapid compared to the time scale at which the disease spreads, then cooperation emerges. Moreover, in the limit as mitigation measures become increasingly effective, the disease can be controlled; the number of infections tends to zero. It has been suggested that disease spreading models may also describe social and group dynamics, indicating that this mechanism for the evolution of cooperation may also apply in those contexts.
... In a scientific brief, dated April 24, 2020, the WHO said, "there is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection" [48]. Several research papers have reported that, even though being infected by the virus may build immunity against the disease in the short-term, it is not a guaranteed fact, and it may not be long-lasting protection [49][50][51]. ...
Background:
COVID-19, a highly infectious disease, was first detected in Wuhan, China, in December 2019, and subsequently spread to 212 countries and territories around the world infecting millions of people. In India, a huge country of about 1.3 billion people, the disease was first detected on 30 January 2020 in a student returning from Wuhan. The total number of confirmed infections in India as of 3 May 2020 is more than 37000, and is currently growing very fast.
Objective:
Most of the prior research and media coverage focused on the number of infections in the entire country. However, given the size and diversity of India, it is important to look at the spread of the disease in each state separately, wherein the situations are quite different. In this article, we aim to analyze data on the number of infected people in each Indian state (restricting to only those states with enough data for prediction) and predict the number of infections for that state in the next 30 days. We hope that such state-wise predictions would help the state governments better channelize their limited healthcare resources.
Methods:
Since predictions from any one model can potentially be misleading, we consider three growth models, namely, the logistic, the exponential, and the susceptible-infectious-susceptible (SIS) models, and finally develop a data-driven ensemble of predictions from the logistic and the exponential models using functions of the model-free maximum daily infection-rate (DIR) over the last two weeks (a measure of recent trend) as weights. The DIR is used to measure the success of the nationwide lockdown. We jointly interpret the results from all models along with the recent DIR values for each state, and categorize the states as severe, moderate or controlled.
Results:
We find that seven states, namely, Maharashtra, Delhi, Gujarat, Madhya Pradesh, Andhra Pradesh, Uttar Pradesh, and West Bengal fall in the severe category. Among the remaining states, Tamil Nadu, Rajasthan, Punjab, and Bihar are in the moderate category, whereas Kerala, Haryana, Jammu and Kashmir, Karnataka, and Telangana are in the controlled category. We also tabulate actual predicted numbers from various models for each state. All the R2 values corresponding to the logistic and the exponential models are above 0.90, indicating a reasonable goodness of fit. We also provide a web-app (https://palash.shinyapps.io/IITG_COVID-19-India/) to see the forecast based on recent data that is updated regularly.
Conclusions:
States with non-decreasing DIR values need to immediately ramp up the preventive measures in order to combat the COVID-19 pandemic. On the other hand, the states with decreasing DIR can maintain the same status to see the DIR slowly become zero or negative for consecutive 14 days to be able to declare the end of the pandemic.
Clinicaltrial:
Not Applicable.
... Algunos estudios al no encontrar anticuerpos en personas recuperadas después de dos meses consideran que los infectados solamente generan inmunidad de corto plazo y por lo tanto no se pudiera pensar en una inmunidad colectiva (Liu et al. 2020, Stringhini et al. 2020. No obstante, un estudio sugirió que los infectados si pueden lograr inmunidad después de superar la infección gracias a la presencia de los productores de anticuerpos, como son los linfocitos (Nelder et al. 2020), quienes actúan como células de memoria cuando están nuevamente en contacto con el virus. ...
Contagio, síntomas y diagnóstico de la COVID-19 en Iquitos-Perú.
The aim was to study SARS-CoV-2 immunity among medical workers in Kazan.
Materials and methods . Studied were serum samples from 348 medical workers from 10 medical organizations in Kazan, divided into groups according to the level of the alleged risk of infection of employees. To determine IgG, a two-stage direct version of the solid-phase ELISA and the test-system “SARS-CoV-2-IgG-ELISA-BEST” (Russia) were used.
Results and discussion . At the time of the study and over the previous three months, the examined medical workers had no symptoms of acute respiratory viral infection or respiratory tract infections; there were negative results of examining nasopharyngeal/ oropharyngeal swabs for the presence of SARS-CoV-2 RNA. Seroprevalence for IgG to SARS-CoV-2 virus for different medical organizations in Kazan ranged within the scope of 3.3–30.8 % and averaged 16.4 %. The wide variation in seroprevalence values in medical workers of different medical organizations may indicate different levels of intensity of professional contacts and the effectiveness of anti-epidemic measures in these medical organizations. Among medical workers with seropositive results, the prevalence of persons with a very high coefficient of positivity (49.1 %) is observed, which characterizes high level of antiviral antibodies. The presence of a high proportion of seropositive individuals among medical workers, who have had an asymptomatic form of COVID-19 confirms the high intensity of the latent epidemic process, which must be taken into account when organizing preventive measures, including vaccination.
Background. The ongoing COVID-19 pandemic generates the urgent need of monitoring the herd immunity among healthcare workers as a high-risk group for infection. Aim. Determining the level and structure of population immunity to SARS-CoV-2 in the medical workers during the second peak of COVID-19 from August to November 2020. Material and methods. The study involved 15,158 medical workers from 91 medical organizations of the Republic of Tatarstan. The age of the examined stuff members varied from 18 to 74 years, the average age was 45.480.1016 years, most of them were women (13 627, 89.870.258%). Testing for the presence of total antibodies (immunoglobulin classes G, A and M) to SARS- CoV-2 was performed once by the enhanced chemiluminescence method. Statistical processing was carried out by methods of variation statistics and correlation analysis according to the Pearson method using MS Excel and WinPepi. Results. Seroprevalence to SARS-CoV-2 in medical workers was 35.230.388%. An increase in seropositive individuals level from 27.440.265% in August to 57.910.499% in November and an increase in the average geometric mean titer of total antibodies (immunoglobulin classes A, M, G) from 84.43 in August to 101.09 in November 2020 were detected. The level of individuals with antibodies increased with age from 18 to 59 years and decreased in group of 6070 years. The largest proportion of seropositive to SARS-CoV-2 individuals was found among junior (42.011.384%) and middle grade (37.50.527%) medical staff of hospitals for patients with COVID-19, ambulance and emergency stations. Among the seropositive to the SARS-CoV-2 workers the proportion of asymptomatic forms of infection was 84.970.498%. According to the level of seroprevalence, municipal districts of the Republic of Tatarstan were divided into three groups: moderate 8.939.0; average 42.949.6, high level 53.164.4. Сonclusion. An increase in seroprevalence to SARS-CoV-2 was revealed among medical workers of the Republic of Tatarstan from August to November 2020 during the second peak of COVID-19.
Objectives
In recent times, researchers have used Susceptible-Infected-Susceptible (SIS) model to understand the spread of the COVID-19 pandemic. The SIS model has two compartments, susceptible and infected. In this model, the interest is to determine the number of infected cases at a given time point. However, it is also essential to know the cumulative number of infected cases at a given time point, which is not directly available from the SIS model's present structure. The objective is to provide a modified SIS model to address that gap.
Methods
In this work, we propose a modified structure of the SIS model to determine the cumulative number of infected cases at a given time point. We develop a dynamic data-driven algorithm to estimate the model parameters based on an optimally chosen training phase to predict the number of cumulative infected cases.
Results
We demonstrate the proposed algorithm's prediction performance using COVID-19 data from Delhi, India's capital city. Considering different time periods, we observed the proposed algorithm’s performance using the modified SIS model is well to predict the cumulative infected cases with two different prediction periods 30 and 40. Our study supports the idea of estimating the modified SIS model's parameters based on the optimal training phase instead of the entire history as the training phase.
Conclusions
Here, we have provided a modified SIS model that accounts for deaths due to disease and predicts cumulative infected cases based on an optimally chosen training phase. The proposed estimation process is beneficial when the disease under study changes its spreading pattern over time. We have developed the modified SIS model considering COVID-19 as the disease under focus. However, the model and algorithms can be applied to predict the cumulative cases of other infectious diseases.
The emergence of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) and its complications have demonstrated the devastating impact of a new infectious pathogen. The organisational change promulgated by the isolation of affected communities is of extreme importance to achieve effective containment of the contagion and good patient care. The epidemiological study of the population of a small rural community in the North East of Italy revealed how much the virus had circulated during Spring, 2020, and how contagion has evolved after a prolonged lockdown. In the 1st phase, NAAT (Nucleic Acid Amplification Testing) was performed in cases with more or less severe symptoms and a study was performed to trace the infection of family members. Only 0.2% of the population tested positive on NAAT, via nasopharyngeal swab during this 1st phase. In the 2nd phase a random sample of the general population were tested for circulating anti-Sars-Cov-2 immunoglobulins. This showed that approximately 97.9% of the population were negative, while 2.1% (with positive IgG at a distance) of the population had contracted the virus in a mildly symptomatic or asymptomatic form. The main symptom in subjects who developed immunity was fever. Antibodies were found in subjects with forced coexistence with quarantined or infected subjects. The mutual spatial distance by categories has shown higher relative prevalence of IgG positive and IgM negative cases in close proximity but also far from the infected, with respect to an intermediate distance. This suggests that subjects living in thinly populated areas could come in contact with the virus more likely due to intentional/relational proximity, while those living nearby could also be infected through random proximity.
Guangdong province, located in South China, is an important economic hub with a large domestic migrant population and was among the earliest areas to report COVID-19 cases outside of Wuhan. We conducted a cross-sectional, age-stratified serosurvey to determine the seroprevalence of antibodies against SARS-CoV-2 after the emergence of COVID-19 in Guangdong. We tested 14,629 residual serum samples that were submitted for clinical testing from 21 prefectures between March and June 2020 for SARS-CoV-2 antibodies using a magnetic particle based chemiluminescent enzyme immunoassay and validated the results using a pseudovirus neutralization assay. We found 21 samples positive for SARS-CoV-2 IgG, resulting in an estimated age- and sex-weighted seroprevalence of 0.15% (95% CI: 0.06–0.24%). The overall age-specific seroprevalence was 0.07% (95% CI: 0.01–0.24%) in persons up to 9 years old, 0.22% (95% CI: 0.03–0.79%) in persons aged 10–19, 0.16% (95% CI: 0.07–0.33%) in persons aged 20–39, 0.13% (95% CI: 0.03–0.33%) in persons aged 40–59 and 0.18% (95% CI: 0.07–0.40%) in persons ≥60 years old. Fourteen (67%) samples had pseudovirus neutralization titers to S-protein, suggesting most of the IgG-positive samples were true-positives. Seroprevalence of antibodies to SARS-CoV-2 was low, indicating that there were no hidden epidemics during this period. Vaccination is urgently needed to increase population immunity to SARS-CoV-2.
Relevance. Age-related and occupational aspects of SARS-CoV-2 seroprevalence in healthcare workers are not well understood . Aims: Conduct a selective study of seroprevalence to the SARS-CoV-2 virus among 348 medical workers of 10 medical organizations in Kazan: seven multidisciplinary hospitals that have been re-profiled to provide medical care to patients with coronavirus infection, an ambulance station, a medical organization that carries out outpatient activities and a specialized clinic. Materials and methods. Among those surveyed on a professional basis, the groups «Doctors», «Nurses», «Junior medical personnel», «Other medical workers» were identified. The age structure of seroprevalence was studied in groups of 18–29, 30–39, 40–49, 50–59 and 60–69 years. For the determination of IgG, a solid-phase ELISA was used. Results. The proportion of medical workers (MR) of various medical organizations in Kazan seropositive for IgG to the SARS-CoV-2 virus is 16.4%. The wide variation in the seroprevalence value of MR groups of different medical organizations (3.3–30.8%) may indicate a different level of effectiveness of anti-epidemic measures in these institutions. The maximum rate was noted in the age groups – 18–29 years (21%) and 60-69 years (18.2%). According to the professional criterion, a comparable level of seroprevalence is shown for the categories «Doctors» and «Nurses» with a wide variation in indicators in professional groups, depending on a particular medical organization. The obtained results indicate the presence among medical workers who have suffered or have an asymptomatic course of infection caused by SARS-CoV-2, and confirm the relevance of further serological monitoring in medical organizations of various profiles. The results of serological monitoring, taking into account age and professional aspects, can serve as the basis for adjusting preventive measures on the basis of individual medical organizations, and taking into account the recommendations of Rospotrebnadzor and the selection of contingents for vaccination against SARS-CoV-2. Conclusions: For the MR of various medical institutions in Kazan, the seroprevalence for antibodies to the SARS-CoV-2 virus is 16.4%; Age aspects affect the level of seroprevalence in MR; The obtained results indicate the presence of persons among MR who have had or have an asymptomatic course of infection caused by SARS-CoV-2, and confirm the relevance of further serological monitoring in medical organizations of various profiles.
In the 1918 influenza pandemic, more than 95% of mortalities were ascribed to bacterial pneumonia. After the primary influenza infection, the innate immune system is attenuated, and the susceptibility to bacteria is increased. Subsequent bacterial pneumonia exacerbates morbidity and increases the mortality rate. Similarly, COVID-19 infection attenuates innate immunity and results in pneumonia. In addition, the current pneumococcal conjugate vaccine may have limited defense against secondary pneumococcal infection after influenza infection. Therefore, until a fully protective vaccine is available, a method of increasing immunity may be helpful. Ginseng has been shown to increase the defense against influenza in clinical trials and animal experiments, as well as the defense against pneumococcal pneumonia in animal experiments. Based on these findings, ginseng is suspected to be helpful for providing immunity against COVID-19.
We have learned to live with many potentially deadly viruses for which there is no vaccine, no immunity, and no cure. We do not live in constant fear of these viruses, instead, we have learned how to outsmart them and reduce the harm they cause. A new mathematical model that combines the spread of diseases that do not confer immunity together with the evolution of human behaviors indicates that we may be able to fight new diseases with the same type of strategy we use to fight viruses like HIV.
The outbreak of coronavirus disease 2019 (COVID-19) is an unprecedented global health crisis. Tissue and peripheral blood analysis indicate profound, aberrant myeloid cell activation, cytokine storm, and lymphopenia, with unknown immunopathological mechanisms. Spatiotemporal control of the quality and quantity of the antiviral immune responses involves synchronized cellular and molecular cascades and cross-talk between innate and adaptive immunity. Dysregulated responses in immunity, such as at the stages of immune sensing, alarming, polarization, and resolution, may contribute to disease pathology. Herein, we approach SARS-CoV-2 through an immunomodulatory lens, discussing possible mechanisms of the asynchronized antiviral immune response and proposing potential therapeutic strategies to correct the dysregulation.
Nearly every vaccine currently approved by the Food and Drug Administration introduces foreign proteins into a healthy but no immune individual. The body’s immune system finds those proteins, which are often part of a pathogen (the measles virus, say), and then quickly learns to recognize them. When the actual virus arrives, your immune system has already been introduced to the offending proteins and knows how to annihilate any living thing that bears them. However, it is different for highly mutated viruses such as COVID -19 and influenza.COVID-19 and influenza viruses have a similar disease presentation. The flu vaccine has to be altered each year to counter changes to circulating strains.In case of COVID-19 there are many factors which can hinder and hamper covid-19 vaccine. Antibody Dependent Enhancement (ADE), a phenomenon in which antibodies to a virus can make a infection worse in some cases, such as with dengue fever, and Frameshift which enables viruses to encode more proteins in spite of their small size in addition the “after” shape and postfusion form of COVID-19 spike protein which is affected by the overall charge and high polarity of COVID-19 genome.One interesting facet of coronaviruses is that they have the largest genomes of any known +RNA viruses.The genome of COVID-19 is protected within a tiny shell, it consists of a single strand of positive polarity RNA (ssRNA +), which is very large compared to other viruses. The “after” shape and postfusion shape of COVID-19 spike protein could induce antibodies that do not neutralize the virus.In effect, the spikes in this forms may act as decoys that distract the immune system.However, because most vaccine and antibody therapies target the trimeric spike protein, any alterations in its genetic sequence could have important implications. Here we will shed light on all these factors which may protect SARS-CoV-2 from our immune system and also, hamper vaccine development against covid-19
An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log 10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.
In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.
Background:
Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.
Methods:
We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.
Results:
The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.
Conclusions:
During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.
Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.
Background:
The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP.
Methods:
We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number.
Results:
Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).
Conclusions:
On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
Background:
An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date.
Methods:
In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done.
Findings:
From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats.
Interpretation:
Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions.
Funding:
The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.
There is a desperate need for effective therapies and vaccines for SARS-CoV-2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked. Here, Iwasaki and Yang highlight the potential dangers of inducing suboptimal antibody responses to SARS-CoV-2. They stress the need for proper safety evaluation of candidate vaccines for COVID-19.
Severe coronavirus disease 2019 (COVID-19) is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Significant antibody production is observed; however, whether this is protective or pathogenic remains to be determined. Defining the immunopathological changes in patients with COVID-19 provides potential targets for drug discovery and is important for clinical management. In the short time since SARS-CoV2 emerged, much has been learned about the immunopathology of the infection. Here, Xuetao Cao discusses what these early insights imply for drug discovery and clinical management.
Background:
To study the clinical data, discharge rate, and fatality rate of COVID-19 patients for clinical help.
Methods:
The clinical data of COVID-19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID-19 patients and explained the discharge rate, fatality rate with a single-arm meta-analysis.
Results:
The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), dyspnea (21.9%). Minor symptoms include headache or dizziness: (12.1%) diarrhea (4.8%), nausea, and vomiting (3.9%). The results of laboratory results showed that the lymphocytopenia (64.5%), increase of CRP (44.3%), increase of LDH (28.3%), and leukocytopenia (29.4%) were more common.
Conclusions:
The results of single-arm meta-analysis showed that: the male took a larger percentage in the gender distribution of COVID-19 patients 60%[95%CI (0.54,0.65)], the discharge rate of COVID-19 patients was 42%[95%CI (0.29,0.55)], and the fatality rate was 7%[95%CI (0.04,0.10)]. This article is protected by copyright. All rights reserved.
An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
Background:
In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed.
Methods:
We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus.
Findings:
The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.
Interpretation:
2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.
Funding:
National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
Background:
In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.
Methods:
In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020.
Findings:
Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure.
Interpretation:
The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection.
Funding:
National Key R&D Program of China.
Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism. Structural analysis of the SARS-CoV S and MERS-CoV S glycoproteins in complex with neutralizing antibodies from human survivors sheds light into the mechanisms of membrane fusion and neutralization
Objectives:
A severe acute respiratory syndrome (SARS)-like disease due to a novel betacoronavirus, human coronavirus EMC (HCoV-EMC), has emerged recently. HCoV-EMC is phylogenetically closely related to Tylonycteris-bat-coronavirus-HKU4 and Pipistrellus-bat-coronavirus-HKU5 in Hong Kong. We conducted a seroprevalence study on archived sera from 94 game-food animal handlers at a wild life market, 28 SARS patients, and 152 healthy blood donors in Southern China to assess the zoonotic potential and evidence for intrusion of HCoV-EMC and related viruses into humans.
Methods:
Anti-HCoV-EMC and anti-SARS-CoV antibodies were detected using screening indirect immunofluorescence (IF) and confirmatory neutralizing antibody tests.
Results:
Two (2.1%) animal handlers had IF antibody titer of ≥ 1:20 against both HCoV-EMC and SARS-CoV with neutralizing antibody titer of <1:10. No blood donor had antibody against either virus. Surprisingly, 17/28 (60.7%) of SARS patients had significant IF antibody titers with 7/28 (25%) having anti-HCoV-EMC neutralizing antibodies at low titers which significantly correlated with that of HCoV-OC43. Bioinformatics analysis demonstrated a significant B-cell epitope overlapping the heptad repeat-2 region of Spike protein. Virulence of SARS-CoV over other betacoronaviruses may boost cross-reactive neutralizing antibodies against other betacoronaviruses.
Conclusions:
Convalescent SARS sera may contain cross-reactive antibodies against other betacoronaviruses and confound seroprevalence study for HCoV-EMC.
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2
- Viruses Csgoticoto
Viruses CSGotICoTo. The species Severe acute respiratory syndrome-related
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