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Study identifies features of potent SARS-CoV-2 neutralizing antibodies - News-Medical.Net
Researchers at Columbia University have provided important insights into features of viral binding and recognition within a class of potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes co…
Researchers at Columbia University have provided important insights into features of viral binding and recognition within a class of potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19). Antibodies with heavy chain regions derived from a gene called VH1-2 constitute some of the most potent neutralizing antibodies against SARS-CoV-2 identified to date. Now, Zizhang Sheng and colleagues have identified shared genetic and structural signatures within a class of VH1-2 antibodies that could improve efforts to elicit such antibody classes through vaccination. A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review. “Multi-donor” antibody classes show potent neutralizing activity against viruses Studies have revealed prominent classes of similar neutralizing antibodies (nAbs) that frequently arise in response to viral infection or vaccination. Such “multi-donor” antibody classes exhibit potent, broad neutralizing activity and frequently occur in the human antibody repertoire. “A prominent mode of rational vaccine design – lineage-based vaccine design – endeavors to elicit such antibody classes by vaccination and this approach has recently entered clinical assessment,” says Sheng and colleagues. The race to develop vaccines against SARS-CoV-2 Since the COVID-19 outbreak began in Wuhan, China, late last year, researchers have been racing to develop effective vaccines that could bring an end to the global public health crisis. In the case of SARS-CoV-2, nAbs primarily target the viral spike protein – the structure that binds the host cell receptor angiotensin-converting enzyme 2 (ACE2) as the initial step in the infection process. The spike protein binds to ACE2 via a region called the receptor-binding domain (RBD). This highly flexible RBD can adopt either an “up” (open) confirmation that is capable of interacting with ACE2 or a “down” (closed) conformation that is not. Many nAbs have been characterized that bind to epitopes on either conformation and neutralize SARS-CoV-2 by competing with ACE2 for RBD binding or locking the RBD in the down conformation. Characterizing genetic features of these nAbs Characterization of the SARS-CoV-2 nAbs so far identified has revealed enrichment of the antibody variable genes VH3-53, VH1-2, VH1-69, VH3-66, VH1-58, and VH3-30. Structural characterization of the various nAbs has revealed two separate RBD-targeted classes that are derived from the similar VH3-53 and VH3-66 genes. One class that is characterized by a heavy chain complementarity-determining region 3 (CDRH3) of 15 amino acids or shorter targets RBD in the up conformation. The other class, which has a longer CDRH3, recognizes a similar region of RBD, suggesting that CDRH3 is critical for the classification of VH3-53/-66 antibodies. More about classes derived from the VH1-2 gene? “Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent SARS-CoV-2-neutralizing antibodies yet identified,” writes Sheng and the team. However, whether these antibodies form gene-restricted classes that represent shared effective antibody responses remains unclear. Currently, three VH1-2 potent nAbs (2-4, S2M11, and C121) have been shown to exhibit similar modes of RBD recognition but different recognition of quaternary epitopes. “It is thus still unclear whether RBD-targeting VH1-2 antibodies form a gene-restricted class,” say the researchers. However, “if so, what are the key genetic and structural signatures and determinants of neutralization potency?” they ask. What did the team do? The researchers determined the structures of three VH1-2-derived antibodies (2-15, 2-43, and H4) in complex with the SARS-CoV-2 spike protein. All three of the antibodies used VH1-2-encoded motifs to recognize the RBD, with a somatic hypermutation (N531) in the heavy chain enhancing binding and light chain tyrosines recognizing the RBD residue F486. Despite these similarities, VH1-2-antibody class members bound both RBD-up and RBD-down conformations, with a subset using elongated CDRH3 to recognize neighboring RBD – a strong quaternary interaction that is critical for locking RBDs in the down conformation. What did the authors conclude? The team says the findings show that the VH1-2 antibody class uses two modules for spike recognition, with the VH1-2 gene-encoded module used to recognize the RBD and the CDRH3 module used for quaternary recognition. “Thus, we define a multi-donor VH1-2 antibody class, members of which can achieve very high neutralization potency, which is prevalent in human responses to SARS-CoV-2,” write the researchers. “The shared genetic and structural signatures inform strategies to improve members of the VH1-2 antibody class,” they conclude. *Important Notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
New N501 SARS-CoV-2 mutation may have been circulating in Italy since August 2020 - News-Medical.Net
A recent study shows that mutated SARS-CoV-2 strains with a substitution at position 501 might have circulated unnoticed even before the end of September 2020, when the rapid emergence of B.1.1.7 lineage (carrying the N501Y mutation) was initially reported.
A recent study published in The Lancet Infectious Diseases journal shows that mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains with a substitution at position 501 might have circulated unnoticed even before the end of September 2020, when the rapid emergence of B.1.1.7 lineage (carrying the N501Y mutation) was initially reported. On December 14 2020, the authorities of the United Kingdom reported to the World Health Organization (WHO) that a new variant of SARS-CoV-2, a causative agent of an ongoing coronavirus disease 2019 (COVID-19) pandemic, was identified through viral genomic sequencing. This variant, often referred to as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01), was shown to spread more readily between people, albeit there are no significant associations with symptom severity or vaccine efficacy. In any case, manifold mutations in the viral spike glycoprotein are characteristic for this variant, with N501Y being a major concern as it involves one of the six key amino acid residues responsible for tight contact between SARS-CoV-2 receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) cellular receptor. Consequently, a group of researchers, led by Dr. Simona Fiorentini from the Department of Molecular and Translational Medicine at the University of Brescia in Italy, conducted detailed metagenomic sequencing and bioinformatic analyses to take a deep look into Italian isolates. Detailed genetic characterization In November 2020, a 59-year-old male individual with a history of persistent SARS-CoV-2 infection underwent molecular testing. Upon laboratory confirmation of the infection, genetic characterization of viruses in November sample or MB61-Nov (but also previous sample from August 2020, known as MB61-Aug) was pursued by metagenomic sequencing. Two complete obtained genomes were subsequently compared with full-length viral genomes freely available on the GISAID platform, which is an open-access source to genomic data of influenza and SARS-CoV-2 viruses. Strains with the mutation N501Y in the spike RBD, which were recently characterized in Italy and the United Kingdom as incorporated to the quickly emerging B.1.1.7 lineage, were included in the analysis. Finally, sequence alignment and detailed editing was also done to obtain the full picture. N501T variants present in early August In short, bioinformatic analyses in this study revealed that the MB61-Aug SARS-CoV-2 isolate had amassed ten amino acid changes compared to early Italian isolates; in addition, three more had appeared along its evolution until the end of November 2020. It has to be noted that the N501T substitution was found in both MB61-Aug and MB61-Nov SARS-CoV-2 isolates, pointing towards the conclusion that a mutation at the key amino acid residue 501 has already been spreading in Italy since August 2020. Our time-scaled maximum likelihood tree suggests that these spike N501T variants emerged in early August in northern Italy, and therefore that SARS-CoV-2 strains harboring a substitution at position 501 might have circulated unnoticed even before the end of September 2020, when the rapidly emerging B.1.1.7 lineage (carrying the N501Y mutation) was first reported", say study authors. The need for a massive research effort Recent discoveries regarding SARS-CoV-2 evolution, particularly within the RBD, warrant a massive scientific effort in order to pinpoint novel variants with the potential of increased viral spreading, but also with the propensity to show an evasive behavior to infection-derived or vaccine-induced neutralizing immunity. This study is one step towards that direction, and it also compared Wuhan reference strain with both MB61 variants. The variants actually carried four mutations and one deletion in the spike glycoprotein – two of which were situated within the RBD. Nonetheless, more complex and lengthy investigations that necessitate collaboration among different research groups will be needed in the future. In that regard, recently established WHO SARS-CoV-2 Virus Evolution Working Group is a way towards improved understanding of this timely issue.
People who take walks in forests or greenspaces may have higher stress coping abilities - News-Medical.Net
Work causes so much stress that it's become a global public health issue. Stress's impact on mental and physical health can also hurt productivity and result in economic loss. A new study now finds that working people who regularly take walks in forests or gr…
Work causes so much stress that it's become a global public health issue. Stress's impact on mental and physical health can also hurt productivity and result in economic loss. A new study now finds that working people who regularly take walks in forests or greenspaces may have higher stress-coping abilities. In a study published in Public Health in Practice, researchers led by Professor Shinichiro Sasahara at the University of Tsukuba analyzed workers' "sense of coherence" (SOC) scores, demographic attributes, and their forest/greenspace walking habits. SOC comprises the triad of meaningfulness (finding a sense of meaning in life), comprehensibility (recognizing and understanding stress), and manageability (feeling equipped to deal with stress). Studies have found factors such as higher education and being married can strengthen SOC, while smoking and not exercising can weaken it. People with strong SOC also have greater resilience to stress. The study used survey data on more than 6,000 Japanese workers between 20 and 60 years old. It found stronger SOC among people who regularly took walks in forests or greenspaces. SOC indicates mental capacities for realizing and dealing with stress. With workplace stress as a focal issue, there's a clear benefit in identifying everyday activities that raise SOC. It seems we may have found one." Shinichiro Sasahara, Professor, University of Tsukuba People find comfort in nature, and in countries like Japan urban greenspaces are increasing in popularity where nature isn't readily accessible. This means many workers in cities can easily take a walk among the trees. The researchers divided the survey respondents into four groups based on their frequency of forest/greenspace walking. Then, they compared their walking activity against attributes such as age, income, and marital status, and with the respondents' SOC scores, which were grouped as weak, middle, and strong. Those with strong SOC showed a significant correlation with both forest and greenspace walking at least once a week. This key finding implies the greater benefits of urban greening--not just environmental, but also socioeconomic. "Our study suggests that taking a walk at least once a week in a forest or greenspace can help people have stronger SOC," explains Professor Sasahara. "Forest/greenspace walking is a simple activity that needs no special equipment or training. It could be a very good habit for improving mental health and managing stress." University of Tsukuba Ikeda, T., et al. (202) Association between forest and greenspace walking and stress-coping skills among workers of Tsukuba Science City, Japan: A cross-sectional study. Public Health in Practice. doi.org/10.1016/j.puhip.2020.100074.
Study shows durable specific humoral immunity against SARS-CoV-2 after mild or asymptomatic infection - News-Medical.Net
As a part of the COMMUNITY (COVID-19 Immunity) study, researchers from Sweden reveal long-lasting IgG neutralizing antibody response against spike glycoprotein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the vast majority of convale…
As a part of the COMMUNITY (COVID-19 Immunity) study, researchers from Sweden reveal long-lasting IgG neutralizing antibody response against spike glycoprotein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the vast majority of convalescent individuals – even after asymptomatic or mild infection. Their results are currently available on medRxiv* preprint server. The expeditious spread of SARS-CoV-2, a causative agent of coronavirus disease (COVID-19), is facilitated by a considerable portion of asymptomatic and pre-symptomatic viral transmission. This is why it is crucial to fully understand the functionality and durability of the immune response against this virus. It is known that antibodies targeting different virus-encoded proteins are key players in conveying protective immunity against SARS-CoV-2. Among the prime targets are spike glycoprotein, which facilitates viral access to the host cell, as well as the highly abundant and conserved nucleocapsid protein. Nonetheless, the duration, kinetics, and efficacy of circulating SARS-CoV-2 antibodies are less familiar, mostly because we are dealing with a new virus. There are actually conflicting studies that show either a rapid decline in circulating IgG antibodies within a few weeks after COVID-19 or their detection up to six months following symptom onset. Hence, understanding the long-term humoral response (which includes virus neutralization capacity) in asymptomatic to mild SARS-CoV-2 infections is pivotal in estimating the immune response on a population basis, possible risk of reinfection, as well as vaccine responses. This is why a research group from Sweden, led by Dr. Sebastian Havervall from the Department of Clinical Sciences at Karolinska Institute in Danderyd Hospital (Stockholm), decided to appraise the duration and efficacy of circulating antibodies four months after infection in a large cohort of patients (primarily healthcare workers). A long-term immunity study This longitudinal cohort study included a total of 1972 healthcare workers, with 386 of them exhibiting antibodies against the SARS-CoV-2 spike glycoprotein antigen at study inclusion. It was conducted as a part of the COMMUNITY (COVID-19 Immunity) study, which is an ongoing investigating of long-term immunity after COVID-19 in Stockholm, Sweden. Venous blood samples were taken at study inclusion and after four months of follow-up. Furthermore, IgG reactivity was measured towards spike glycoprotein trimers entailing the prefusion-stabilized spike ectodomain and the C-terminal domain of the nucleocapsid protein. Microneutralization assay was utilized, and cells were inspected by optical microscopy after four days. In cases when less than 50% of the cell layer showed signs of the cytopathogenic effect (i.e., structural changes of the host cell due to viral invasion), the well was regarded as neutralizing. Seroconversion was associated with prior COVID-19 symptoms Seroconversion to anti-spike IgG (purple) and anti-nucleocapsid IgG (orange) prior to study inclusion (circles) and during the follow-up period (triangles) was associated with self-reported anosmia, ageusia, fever, muscle or joint pain, presence of any symptoms, malaise, cough, headache, abdominal symptoms, dyspnea, or runny nose. CI: Confidence Interval. Highly persistent neutralizing antibodies In short, this study has shown that the vast majority of healthcare workers (98% of them) remained seropositive for SARS-CoV-2 anti-spike IgG at least four months after the infection, regardless of having mild symptoms or no symptoms at all. Moreover, antibody levels were no different from 59 convalescent patients suffering from severe to critical COVID-19. The researchers have also corroborated earlier findings of strong concordance between SARS-CoV-2 anti-spike IgG levels and virus neutralization capacity – supporting, in turn, an enduring immunity after COVID-19 even in asymptomatic individuals or those with mild symptoms. Conversely, anti-nucleocapsid IgG levels declined to an undetectable range in 32% of the study participants with mild infection (or without symptoms), emphasizing the importance of diligent antigen selection for any test or survey. Implications of the findings "Taken together, our findings imply a strong and long-lasting humoral immune response against SARS-CoV-2, even after asymptomatic or mild infection", conclude the authors of this medRxiv paper. Furthermore, demonstrated differences in antibody kinetics in dependence on the antigen is basically an argument against the use of the nucleocapsid protein as a possible target antigen in population-wide SARS-CoV-2 serological surveys and analyses. Everything said, these findings are indeed highly relevant for understanding correlates of long-term humoral immunity after SARS-CoV-2 infection, which is necessary for public health planning, the evaluation of potential reinfection risk, as well as for long-term vaccine response appraisal. *Important Notice medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Researchers discover how shattered chromosomes make cancer cells more aggressive - News-Medical.net
Cancer is one of the world's greatest health afflictions because, unlike some diseases, it is a moving target, constantly evolving to evade and resist treatment.
Cancer is one of the world's greatest health afflictions because, unlike some diseases, it is a moving target, constantly evolving to evade and resist treatment. In a paper published in the December 23, 2020 online issue of Nature, researchers at University of California San Diego School of Medicine and the UC San Diego branch of the Ludwig Institute for Cancer Research, with colleagues in New York and the United Kingdom, describe how a phenomenon known as "chromothripsis" breaks up chromosomes, which then reassemble in ways that ultimately promote cancer cell growth. Chromothripsis is a catastrophic mutational event in a cell's history that involves massive rearrangement of its genome, as opposed to a gradual acquisition of rearrangements and mutations over time. Genomic rearrangement is a key characteristic of many cancers, allowing mutated cells to grow or grow faster, unaffected by anti-cancer therapies. "These rearrangements can occur in a single step," said first author Ofer Shoshani, PhD, a postdoctoral fellow in the lab of the paper's co-senior author Don Cleveland, PhD, professor of medicine, neurosciences and cellular and molecular medicine at UC San Diego School of Medicine. "During chromothripsis, a chromosome in a cell is shattered into many pieces, hundreds in some cases, followed by reassembly in a shuffled order. Some pieces get lost while others persist as extra-chromosomal DNA (ecDNA). Some of these ecDNA elements promote cancer cell growth and form minute-sized chromosomes called 'double minutes.'" Research published last year by scientists at the UC San Diego branch of the Ludwig Institute for Cancer Research found that up to half of all cancer cells in many types of cancers contain ecDNA carrying cancer-promoting genes. In the latest study, Cleveland, Shoshani and colleagues employed direct visualization of chromosome structure to identify the steps in gene amplification and the mechanism underlying resistance to methotrexate, one of the earliest chemotherapy drugs and still widely used. In collaboration with co-senior author Peter J. Campbell, PhD, head of cancer, aging and somatic mutation at Wellcome Sanger Institute in the United Kingdom, the team sequenced the entire genomes of cells developing drug resistance, revealing that chromosome shattering jump-starts formation of ecDNA-carrying genes that confer anti-cancer therapy resistance. The scientists also identified how chromothripsis drives ecDNA formation after gene amplification inside a chromosome. Chromothripsis converts intra-chromosomal amplifications (internal) into extra-chromosomal (external) amplifications and that amplified ecDNA can then reintegrate into chromosomal locations in response to DNA damage from chemotherapy or radiotherapy. The new work highlights the role of chromothripsis at all critical stages in the life cycle of amplified DNA in cancer cells, explaining how cancer cells can become more aggressive or drug-resistant." Ofer Shoshani, Ph.D., First Author Said Cleveland: "Our identifications of repetitive DNA shattering as a driver of anti-cancer drug resistance and of DNA repair pathways necessary for reassembling the shattered chromosomal pieces has enabled rational design of combination drug therapies to prevent development of drug resistance in cancer patients, thereby improving their outcome." The findings address one of the so-called nine Grand Challenges for cancer therapy development, a joint partnership between the National Cancer Institute in the United States and Cancer Research UK, the world's largest independent cancer research and awareness charity. University of California - San Diego Shoshani, O., et al. (2020) Chromothripsis drives the evolution of gene amplification in cancer. Nature.doi.org/10.1038/s41586-020-03064-z.
Epitope “megapools” could help determine role T cell immunity plays in COVID-19 - News-Medical.Net
Researchers in the United States and Australia have conducted a comprehensive analysis of the epitope recognition patterns associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans.
Researchers in the United States and Australia have conducted a comprehensive analysis of the epitope recognition patterns associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. The SARS-CoV-2 virus is responsible for the coronavirus disease 2019 (COVID-19) pandemic that currently has scientists racing to develop effective vaccines and antiviral therapies. The team – from La Jolla Institute for Immunology (LJI) in California, the University of California San Diego (UCSD), and Murdoch University, Perth – identified hundreds of human leukocyte antigen (HLA) class I and HLA class II-restricted SARS-CoV-2-derived epitopes. The study revealed distinct patterns of SARS-CoV-2 immunodominance that differed between CD4+ T cells, CD8+ T cells, and antibodies. Alessandro Sette and colleagues say that to their knowledge, no study to date has described the repertoire of CD4+ and CD8+ T cell SARS-CoV-2 epitopes with a comparable level of granularity or breadth. The team combined these epitopes to create new epitope “megapools” that can be used to measure virus-specific CD4+ and CD8+ T cell responses and could facilitate research into the role that T cell immunity plays in SARS-CoV-2 infection and COVID-19. A pre-print version of the paper is available on the bioRxiv* server, while the article undergoes peer review. T cell responses appear to modulate COVID-19 severity The disease course following SARS-CoV-2 infection is highly variable, ranging from mild or even asymptomatic, to severe viral pneumonia, respiratory distress and multi-organ damage. A growing body of evidence points to SARS-CoV-2-specific T cell responses as key modulators of this disease severity. Mild COVID-19 has been associated with coordinated antibody, CD4+ T cell and CD8+ T cell responses, while severe cases have been associated with a lack of coordination in cellular and antibody responses. To date, most studies aiming to delineate the role that T cell responses play have used pools of predicted or overlapping peptides that span the sequence of different SARS-CoV-2 antigens. However, the exact T cell epitopes and immunodominant antigen regions involved have not been fully determined. “Defining a comprehensive set of epitope specificities is important for several reasons,” write the researchers. For example, the ability to determine whether certain regions within different SARS-CoV-2 antigens are immunodominant would be key to ensuring vaccine constructs not only include regions targeted by neutralizing antibodies, but also those capable of delivering sufficient T cell responses. Furthermore, a comprehensive survey of SARS-CoV-2-derived epitopes restricted by a set of different HLAs that are diverse across the general population would help to ensure study findings are generalizable to different ethnicities. What did the researchers do? To identify the pattern of immunodominance across the various SARS-CoV-2 antigens and quantify CD4+ and CD8+ T cell responses to the virus, the team studied epitope-specific T cell responses using peripheral blood mononuclear cell (PBMC) samples taken from 99 adult convalescent COVID-19 donors. The SARS-CoV-2 proteome was probed using 1,925 different overlapping peptides that spanned the entire viral genome, to ensure unbiased coverage of the different HLA class II alleles expressed across the study cohort. For HLA class I, the team selected an additional 5,600 predicted binders for 28 prominent HLA class I alleles, representing 98.8% of HLA class I coverage worldwide. “We are not aware of any study that describes the repertoire of CD4+ and CD8+ T cell epitopes recognized in SARS-CoV-2 infection with a comparable level of granularity or breadth,” writes the team. What did they find? The researchers identified several hundred HLA-restricted SARS-CoV-2-derived epitopes. They observed clear patterns of immunodominance that differed between CD4+ T cells, CD8+ T cells, and antibodies. A limited number of antigens accounted for around 80% of the total response and overall, the same antigens were dominant for both CD4+ and CD8+ responses. However, HLA binding capacity was a major determinant of immunogenicity for CD4+ T cells. “Binding to multiple HLA allelic variants is an important mechanism to amplify the potential immunogenicity of peptide epitopes and specific regions within an antigen,” says Sette and colleagues. Next, the team projected the CD4+ T cell dominant regions onto known or predicted SARS-CoV-2 protein structures. This revealed that the dominant epitope regions are different for B and T cells. “This is of relevance for vaccine development, as inclusion of antigen sub-regions selected on the basis of dominance for antibody reactivity might result in an immunogen devoid of sufficient CD4+ T cell activity,” writes the team. Unlike the clearly distinct dominant regions observed for CD4+ T cell and antibody responses, CD8+ T cell epitopes were distributed uniformly throughout the various antigens, suggesting little positional effect in CD8+ T cell epitope distribution. “In the case of CD8+ T cell responses, our data highlights HLA-allele specific differences in the frequency and magnitude of responses,” writes the team. “Our study provides a roadmap for inclusion of specific regions or discrete epitopes, to allow for CD8+ T cell epitope representation across a variety of different HLAs.” Combining the epitopes into megapools Overall, these experiments identified a total of 280 CD4+ and 454 CD8+ T cell epitopes, which the researchers combined into new epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4+ and CD8+ T cells. We plan to make these epitope pools available to the scientific community at large, and expect that they will facilitate further investigation of the role of T cell immunity in SARS-CoV-2 infection and COVID-19,” says Sette and colleagues. The researchers anticipate that the study findings will be of significant value for helping to understand immune responses to SARS-CoV-2 infection and for developing T-cell-based diagnostics. “In addition, the results shed light on the mechanisms of immunodominance of SARS-CoV-2, which have implications for understanding host-virus interactions, as well as for vaccine design,” they conclude. *Important Notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Phycobilins found to inhibit SARS-CoV-2 enzymes in vitro - News-Medical.Net
Researchers have released an interesting new study that describes the broad-spectrum of antiviral activity that phycobilins can have. Phycobilins, which are bioactive plant compounds, were found to inhibit two coronavirus enzymes.
The search for effective antivirals to counter or prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the pathogen that causes coronavirus disease 2019 (COVID-19), continues. Researchers from Tennesee State University and Meharry Medical College in the United States have released an interesting new study on the preprint bioRxiv* server in November 2020 that describes the broad-spectrum of antiviral activity that phycobilins can have. Phycobilins, which are bioactive plant compounds, were found to inhibit two coronavirus enzymes. Seven viruses from the coronavirus family are known to cause infectious human disease, four of them causing seasonal common colds, and three causing potentially lethal respiratory syndromes. Among the latter three, SARS-CoV-2 has already killed over 1.42 million people worldwide within a year, while the number of infections globally has crossed 60.5 million. COVID-19 has proved difficult to contain because of SARS-CoV-2’s high transmissibility and a lack of vaccines or therapeutic agents that can effectively fight against it. While many old and new drugs are being tried out, there is a severe lack of clinical data on which to base treatment decisions. The current study is an example of an approach that focuses on identifying broad-spectrum antivirals that can inhibit not just this virus but a range of others, both coronaviruses and other novel viral pathogens. Broad-spectrum antivirals Broad-spectrum antivirals (BSA) fall into one of two classes: those which inhibit viral entry by engaging viruses before they enter the host cell, and those which prevent viral replication such that the virus within the host cell cannot initiate productive infection. In the case of coronaviruses, the spike (S) protein differs significantly between the other human coronaviruses and is therefore not a fit target for the first class of BSA. However, the coronavirus nonstructural proteins (nsps) that are key to viral replication are highly conserved; their structure remaining the same between different viruses of this family. Several researchers have reported SARS-CoV-2 nsps that can be targeted by antivirals, including the main protease MPro, the papain-like protease PLPro, RNA dependent RNA polymerase RdRp, and nsps 14-16. Among these, MPro and PLPro cleave viral polyproteins into functional nsps. MPro acts on 11 or more cleavage sites of replicase 1ab. At the same time, PLPro catalyzes proteolysis of the peptide linkage at the P1 position to produce nsps 1, 2 and 3, all of which are essential for viral replication. The study The current study focuses on phytochemicals, which are less toxic than synthetic drugs in many cases, and have been reported to have antiviral activity against multiple viruses, including coronaviruses. Selecting 15 phytochemicals of various chemical classes based on existing knowledge of their antiviral activity, the researchers studied their binding interactions with the SARS-CoV-2 MPro and PLPro. These compounds include flavonols like quercetin, flavins like riboflavins, isoflavones such as daidzein and genistein, phenolic ketones like gingerol, and phenolic alkaloids such as capsaicin, all of which are well-known plant compounds. The study’s findings Their interactions with the viral enzymes were examined by docking studies. These showed that the phycobilins (PCB) docked with the best score or binding energy for MPro, followed by riboflavin, cyanidin, daidzein and genistein in a close cluster. There were 12 important residues at the active site involved in these interactions with the phytochemicals. The docking studies for PLPro were carried out in dimer form, when PCB again had the best score and binding energy. This involved 11 key residues in chain A and 13 in chain B of the enzyme. These in silico experiments were validated by in vitro studies comparing the potential inhibitors with established inhibitory compounds for each of the enzymes. With the positive control containing the enzyme without the inhibitor, its activity was set at 100%. The six phytochemicals with the best docking score, as mentioned above, were tested against MPro. In the first phase, PCB was found to have the highest inhibitory activity, with half-maximal inhibitory concentration (IC50) less than half that of the second-place quercetin (71 versus 145 μM). Again, for PLPro, four of these compounds were screened, again showing PCB to have the most potent inhibitory activity with IC50 of 62 μM. Thus, PCB is shown to have powerful inhibitory activity against both these enzymes. The ability of PCB to inhibit other coronavirus MPro and PLPro enzymes was assessed using the crystal structures of these enzymes in various human and animal coronaviruses. Docking studies were carried out on both dimeric and monomeric forms. PCB was found to have a high docking affinity for MERS MPro and PLPro. However, for the latter, the dimeric form of the enzyme had a higher binding affinity relative to the monomeric enzyme. When only monomers were compared, the highest docking score for PCB was with MERS-CoV, TGEV and SARS-CoV-2, indicating its potential to be a broad-spectrum inhibitor. When other phycobilins, such as phycourobilin (PUB), Phycoerythrobilin (PEB) and Phycoviolobilin (PVB), were explored, they all bound strongly to the binding pockets of these enzymes at specific amino acids, with PCB having the highest or almost the highest docking score for both enzymes. It is notable that these compounds also have other powerful therapeutic properties such as scavenging oxidative radicals, inhibiting cancer cell division and platelet aggregation. They can also be used orally in the form of the phycobilin-protein complex, phycobiliprotein. Once ingested, it is digested in the human gut, and free PCB is released there, which may account for the therapeutic properties of this complex. Conclusion The researchers call for “in-vivo studies on inhibition of CoVs infectivity using human cells and animal models.” Moreover, they suggest that more phycobilin lead compounds could be developed by structure-guided development to “rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-associated diseases.” *Important Notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
COVID-19 potentially has negative impacts on male fertility - News-Medical.Net
A review recently published in the Journal of Medical Virology has discussed some of the effects that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19) – may have on male fe…
A review recently published in the Journal of Medical Virology has discussed some of the effects that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19) – may have on male fertility. In the paper, Cemile Seymen from Gazi University Institute of Health Sciences, in Ankara, Turkey, summarizes study findings showing how the infection can negatively affect male reproductive health. Seymen says further studies are needed to investigate the roles that the host cell proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) may play in infection since both of these proteins, which are involved in viral entry, are highly expressed in the male reproductive system. Very little data are available on the effects of COVID-19 on male fertility Since SARS-CoV-2 was first identified in Wuhan, China, late last year (2019), studies have shown that the virus not only causes respiratory disease but can affect various different organs, including those of the male reproductive system. "There is a very limited number of data about the effects of COVID-19 on male fertility, so it has become an important topic for researchers," says Seymen. ACE2 is highly expressed in the male genital tract To gain viral entry, SARS-CoV-2 uses a surface structure called the spike protein to bind to the ACE2 receptor present on host cells. One study published earlier this year showed that ACE2 messenger RNA was expressed in both germ and somatic cells of the testis. Other studies have found that ACE2 is expressed in spermatogonia, Leydig cells, and Sertoli cells. One study that used electron microscopy to examine post-mortem tissues from the testes of twelve COVID-19 patients demonstrated swelling, vacuolation, and cytoplasmic dilution in the Sertoli cells and a reduction in the number of Leydig cells, compared with patients who did not have COVID-19. Some studies have also demonstrated increased levels of the autophagy receptor SQSTM1 in cells infected with SARS-CoV-2, indicating a fall in autophagy flux. "As a result, SARS-CoV-2 may cause male reproductive disorders by regulating the level of autophagy in male germ cells," writes Seymen. Researchers have also proposed that an increase in testicular temperature as an indirect effect of inflammation has negative impacts on the testes among COVID-19 patients. What about TMPRSS2? Seymen also discusses the role that TMPRSS2 may play in SARS-CoV-2 infection of the prostate. One study found that this enzyme, which cleaves the spike protein in preparation for virus and host membrane fusion, is highly expressed in the prostate's epithelium. This gland secretes prostate fluid, one of the main components of the seminal fluid. Muscles within the gland are responsible for pushing the seminal fluid through the urethra during ejaculation. The high expression of TMPRSS2 within the prostate could increase the likelihood of SARS-CoV-2 infection in this gland, which may affect its ability to secrete these fluids, says Seymen. Effects on the nervous system could affect male fertility Seymen points out that SARS-CoV-2 could also exert negative impacts on male fertility indirectly, through mechanisms involving the nervous system. For example, most viruses permeate the blood-brain barrier and reports have shown that glial cells and neurons also express ACE2 receptors, potentially making them a target for neuronal death induced by SARS-CoV-2. Importantly, the central nervous system plays a critical role in endocrine control and spermatogenesis. Neurons in the hypothalamus secrete gonadotropin-releasing hormone (GnRH), for example, which triggers the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. Low levels of GnRH results in decreased FSH and LH, which in turn impacts the function of Sertoli cells and Leydig cells. Seymen also points out that depression and anxiety (which many people are experiencing during the current pandemic) are associated with increased levels of cortisol and prolactin, as well as a lower sperm count and semen volume, all of which have been shown to contribute to sexual dysfunction. Further studies are needed Seymen says that taken together, these study findings suggest that the COVID-19 pandemic affects the male reproductive system in both direct and indirect ways. "Additional studies are necessary to answer all the questions and further investigations are warranted, but ACE2 and TMPRSS2 play an important role in the cellular entry of SARS-CoV-2. Because the male genital system presents high ACE 2 expression, the importance of this pathway increases in COVID-19 cases," she concludes.
Seroprevalence meta-analysis predicts 643 million already infected by SARS-CoV-2 globally - News-Medical.Net
A recent systematic review and meta-analysis conducted by a team of international scientists reveal low seroprevalence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in the general population.
A recent systematic review and meta-analysis conducted by a team of international scientists reveal low seroprevalence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in the general population. According to the study’s findings, estimating seroprevalence may be a better approach to complement SARS-CoV-2 infection testing and to ascertain a more accurate picture of the global burden of the pandemic. The study is currently available on the medRxiv* preprint server. Since its emergence in December 2019, the highly infectious SARS-CoV-2, the causative pathogen of coronavirus disease 2019 (COVID-19), has infected more than 56.5 million people and claimed more than 1.35 million lives worldwide. Although several measures have been taken to improve the quality and quantity of testing, the exact global prevalence of SARS-CoV-2 infection seems to be higher than the reported prevalence because of limited availability and accessibility of testing in socioeconomically deprived countries. Moreover, an increased prevalence of asymptomatic cases could be another significant reason for such underestimated COVID-19 incidence. Diagnosis of COVID-19 is most commonly done by rapid antigen testing or polymerase chain reaction (PCR)-based viral RNA testing using nasopharyngeal swabs or saliva samples. In contrast, an antibody assay is generally performed to determine the presence of anti-SARS-CoV-2 antibodies in blood samples. A positive antibody test indicates past SARS-CoV-2 infection in non-vaccinated people. Hence, serological antibody testing provides a more accurate estimation of previous infections in the general population. Many studies have been done nationally as well as regionally to estimate the seroprevalence of SARS-CoV-2 antibodies in the general population. These seroepidemiological studies are particularly important for identifying high-risk groups. Population-based seroepidemiological data can be used as a reference to optimally strategize public health measures and the distribution of COVID-19 vaccines. Current study design The scientists systematically reviewed and analyzed many seroepidemiological study findings to more accurately estimate the global prevalence of SARS-CoV-2 infection. Their search included peer-reviewed articles, preprint articles, and other non-commercial/non-academic articles that were published between January 1 and August 28, 2020. They used various statistical analytical methods to identify demographic differences in seroprevalence and study-level factors associated with seroprevalence. To better estimate the global seroprevalence, they corrected available study findings for test sensitivity and specificity. Important observations A total of 338 seroepidemiological studies were analyzed. These studies involved 2.3 million individuals from 50 countries. About 54% and 46% of the studies were conducted in the general population and special populations (specific occupation, health status, and COVID-19 exposure status), respectively. The current study analysis revealed that the SARS-CoV-2 antibody seroprevalence was as low as 3.2% in the general population. Similarly, the seroprevalence was 5.4% in at-risk populations (special populations). Regarding frontline workers, the presence of anti-SARS-CoV-2 antibodies were detected in 6.3% and 10% of healthcare workers and essential non-healthcare workers, respectively. Compared to the general population, healthcare workers were 1.7 times more likely to be seropositive. Similarly, people with established contact exposure were also susceptible to develop anti-SARS-CoV-2 antibodies. A comparatively lower seroprevalence was observed in high-income countries (3.4%). However, differences in estimated seroprevalence were observed in low- and middle-income WHO Global Burden of Disease (GBD) regions, ranging from 1.0% in Southeast Asia, East Asia, and Oceania to 18.8% in South Asia. Despite having a higher risk of SARS-CoV-2 transmission and poor COVID-19 prognosis, the number of studies conducted in low- and middle-income countries was low (25%). Regarding demographic characteristics, a higher seroprevalence is observed in people ages 18 to 64 years compared to those ages 65 years and above. White people were less likely to have anti-SARS-CoV-2 antibodies than black people and Asian people. Most importantly, the scientists observed that the seroprevalence estimates were 14.5 times higher than the corresponding collective prevalence of COVID-19 cases. This difference became more noticeable when local seroprevalence studies were included for analysis. Relatively higher frequencies of local studies conducted in COVID-19 hotspots may be the reason for such discrepancy. Overall, these findings indicate that estimating only confirmed COVID-19 cases is not sufficient to determine the actual burden of SARS-CoV-2 infection. By analyzing seroprevalence to collective COVID-19 incidence ratios, the scientists indicate that about 643 million people may have already been infected by SARS-CoV-2 globally, which is much more than the reported COVID-19 cases (currently 56.5 million).
Domestic cats can be asymptomatic carriers of SARS-CoV-2, show studies - News-Medical.Net
Two recently published studies from Kansas State University researchers and collaborators have led to two important findings related to the COVID-19 pandemic: Domestic cats can be asymptomatic carriers of SARS-CoV-2, but pigs are unlikely to be significant ca…
Reviewed by Emily Henderson, B.Sc.Nov 19 2020 Two recently published studies from Kansas State University researchers and collaborators have led to two important findings related to the COVID-19 pandemic: Domestic cats can be asymptomatic carriers of SARS-CoV-2, but pigs are unlikely to be significant carriers of the virus. SARS-CoV-2 is the coronavirus responsible for COVID-19. Other research has shown that COVID-19-infected human patients are transmitting SARS-CoV-2 to cats; this includes domestic cats and even large cats, such as lions and tigers. Our findings are important because of the close association between humans and companion animals." Jürgen A. Richt, Regents Distinguished Professor, Kansas State University, College of Veterinary Medicine There are about 95 million house cats in the U.S. and about 60 million to 100 million feral cats, Richt said. Richt is the senior author on the two recent collaborative publications in the journal Emerging Microbes & Infections: "SARS-CoV-2 infection, disease and transmission in domestic cats" and "Susceptibility of swine cells and domestic pigs to SARS-CoV-2." Through their in-depth study at the K-State Biosecurity Research Institute, or BRI, at Pat Roberts Hall, the researchers studied susceptibility to infection, disease and transmission in domestic cats. They found that domestic cats may not have obvious clinical signs of SARS-CoV-2, but they still shed the virus through their nasal, oral and rectal cavities and can spread it efficiently to other cats within two days. Further research is needed to study whether domestic cats can spread the virus to other animals and humans. "This efficient transmission between domestic cats indicates a significant animal and public health need to investigate a potential human-cat-human transmission chain," said Richt, who is also the director of the university's Center of Excellence for Emerging and Zoonotic Animal Diseases, known as CEEZAD, and the Center on Emerging and Zoonotic Infectious Diseases, known as CEZID. For the study involving pigs, the researchers found that SARS-CoV-2-infected pigs are not susceptible to SARS-CoV-2 infection and do not appear to transmit the virus to contact animals. "Pigs play an important role in U.S. agriculture, which made it important to determine the potential SARS-CoV-2 susceptibility in pigs," Richt said. "Our results show that pigs are unlikely to be significant carriers of SARS-CoV-2." The BRI has provided the high-security laboratories for Richt and collaborators to study SARS-CoV-2. It is a biosafety level-3 and biosafety level-3 agriculture facility that houses important multidisciplinary research, training and educational programs on pathogens that affect animals, plants and insects, as well as food safety and security. Richt and his collaborators plan further studies to understand SARS-CoV-2 transmission in cats and pigs. They also plan to study whether cats are immune to SARS-CoV-2 reinfection after they have recovered from a primary SARS-CoV-2 infection. "This research is important for risk assessment, implementing mitigation strategies, addressing animal welfare issues, and to develop preclinical animal models for evaluating drug and vaccine candidates for COVID-19," Richt said.
Hydrogen therapy may help severely ill COVID-19 patients - News-Medical.Net
Researchers from the Department of Critical Care Medicine, Sichuan Provincial People's Hospital, Chengdu in China, have explored the possibility of using hydrogen therapy on severely ill COVID-19 patients. The team published their study's findings, titled "Hy…
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, has infected over 55.1 million people around the world, and severe forms of the disease have caused more than 1.31 million deaths. As yet, no specific and effective antiviral drugs are available to treat the severe form of the disease. Similarly, no effective and safe vaccines that could immunize against SARS-CoV-2 are available for use by the general population and those vaccine candidates currently entering their final stages of approval may not be widely distributed for some time. Researchers from the Department of Critical Care Medicine, Sichuan Provincial People's Hospital, Chengdu in China, have explored the possibility of using hydrogen therapy on severely ill COVID-19 patients. The team published their study's findings, titled "Hydrogen: A Potential New Adjuvant Therapy for COVID-19 Patients," in the latest issue of the journal Frontiers in Pharmacology. Background The authors explained that hydrogen possesses properties such as antioxidant, anti-inflammatory and hormone-regulating actions. It can also help resist immune-led apoptosis (or programmed cell death) among cells of the body. SARS-CoV-2 is known to cause cytokine storms or severe inflammatory action in some individuals. This form of cytokine storms is often seen in severe COVID-19 cases and can often result in fatalities. Cytokine storms are known to cause damage to the lungs. Hydrogen therapy, the researchers write, is known to cause "ropy sputum drainage," which reduces the intensity of the disease and can also help as an adjuvant therapy in severe disease. Inflammatory markers In severe COVID-19, the team explains, there is a marked rise in plasma levels and of inflammatory markers such as IL-2 (Inter Leukin), IL-7, IL-10, and TNF- (Tumor necrosis factor). At present, cytokine storms where these features are seen, have no specific treatments. Hydrogen therapy The team writes that hydrogen is a "colorless, odorless, and tasteless gas." In 2007, a study published in Nature, showed that inhalation of two percent hydrogen could specifically eliminate the hydroxyl radical (OH) and peroxynitrite anion (ONOO). Among rats with ischemic injury to the brains, this inhalation could help in reperfusion and correction of ischemic injury, found the researchers. The researchers of the present study note that since then, hydrogen therapy has gathered a lot of interest among researchers and critical care specialists. The team writes that hydrogen has properties such as "anti-oxidation, anti-inflammation, anti-apoptosis, and hormone regulatory" and thus could potentially find utility in several diseases. Moreover, being small, the hydrogen molecule is capable of reaching the alveoli and thus could help in lung diseases, Cytokine storm In cytokine storms, there is a rise in pro-inflammatory cells and mediators called cytokines such as tumor necrosis factor- (TNF-), interleukins (such as IL-1 and IL-6), and interferon- (IFN-). Once activated, these cytokines activate the NADPH oxidase in leukocytes or white blood cells. This, in turn, gives rise to reactive oxygen species (ROS), including "superoxide, hydroxyl radicals, and singlet oxygen." These are known to cause damage to several organs. SARS-CoV-2 induces an interferon--related cytokine storm that leads to severe disease. This form of cytokine storm has also been seen in avian influenza A H5N1 (caused by high viral loads) and Middle East respiratory syndrome (MERS), a betacoronavirus in the same family as SARS-CoV-2. It is usually caused due to high IL-1 , INF-, IP-10, MCP-1, G-CSF, MIP-IA and TNF-. Hydrogen as treatment option As treatment options for severe COVID-19, several drugs are being tried, including tocilizumab and dexamethasone. Studies have also tried anti-IL6-receptor therapy among these patients. Some researchers have also found that hydrogen can suppress the inward infiltration of the WBCs such as neutrophils and macrophages in lung tissue and also block the action of NF-B and MPO in lung tissue. It reduces the inflammatory factors and also reduces the cytokine secretion in lung tissue, including TNF-, IL-1, IL-6, and HMGB1. Hydrogen also removes the ROS, including hydroxyl and peroxynitrate anions and restores normal metabolism of the redox reactions and other ROS. Thus studies have shown, wrote the researchers, "hydrogen treatment can reduce the levels of TNF-, IL-1, IL-1 , IL-6, IL-8, HMGB1, CCL2, and Egr-1 in lung tissue in an animal model". In 45 minutes, hydrogen inhalation can reduce the airway inflammation seen among asthma and COPD patients. The team added, "hydrogen can inhibit the Rho/ROCK pathway, increase the expression of ZO-1, and protect lung tissue cells by improving cell-to-cell permeability, and reducing lung injury." They thus speculate that hydrogen could play a role in therapy for severe COVID-19 patients with lung injury. Hydrogen and its effects on oxidative stress Superoxide dismutase (SOD) is an enzyme that works by protecting the body against antioxidant damage, explain the researchers. Hydrogen therapy has been found to reduce the amounts of malondialdehyde in lung tissues and thus increase the action of SOD. The researchers state that critically ill COVID-19 patients often develop multiple organ failure and that hydrogen, due to its properties of antioxidation and anti-apoptosis, could help protect several organs in the body, including the heart, the kidneys and the nervous system. Hydrogen reduces the viscous secretions seen in COVID-19 In lung injuries caused by inflammation, viscous secretions fill up the alveoli and clog up the terminal bronchi. Oxygen use given using nasal high-flow oxygen inhalation and non-invasive ventilator-assisted ventilation can help the patients. The researchers added that this positive pressure ventilation mode could also lead to the accumulation of viscous bronchial secretions and ultimately worsen the hypoxia or lack of oxygen at the terminal bronchi. Hydrogen-enriched water, when used in mucus secretion in smog-induced COPD models of rats, has shown that there is reduced secretion and relief of hypoxia. The team writes, "early hydrogen inhalation may promote sputum dilution, improve small airway resistance, and relieve dyspnea." How safe is hydrogen therapy? Some of the safety concerns include the fact that it is flammable and explosive, but less than 4 percent together with oxygen at room temperature is not combustible. No serious side effects are seen with hydrogen use. Some complain of heartburn, constipation and headache. The authors believe that hydrogen therapy could be used among severe COVID-19 patients with success. They write, "In the future, more large-scale randomized controlled trials are needed to verify the efficacy and safety of this treatment clinically."
COVID-19 outbreak on an American aircraft carrier: A case study in transmission - News-Medical.Net
A new study showing the dynamics of infectious spread within close quarters of an aircraft carrier. The study presents a rich case study that may help us better understand the dynamics of SARS-CoV-2’s transmission and thereby fine-tune present policies that a…
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19) – is a highly infectious pathogen that spreads from human to human in close quarters. A new study, entitled “An Outbreak of Covid-19 on an Aircraft Carrier”, has published in the New England Journal of Medicine (NEJM), showing the dynamics of infectious spread within close quarters of an aircraft carrier. The study presents a rich case study that may help us better understand the dynamics of SARS-CoV-2’s transmission and thereby fine-tune present policies that aim to prevent its spread. This study was also conducted, say the researchers, to evaluate the epidemiology and outcomes of SARS-CoV-2 infection among “healthy, fit, military-aged adults” confined in close quarters. The aircraft carrier and COVID-19 The U.S.S. Theodore Roosevelt, a nuclear-powered aircraft carrier with 4,779 personnel on board, was on the western Pacific Ocean when an outbreak of COVID-19 cases occurred. Once the outbreak was detected, the ship was moved to U.S. Naval Base Guam. This base had a 42-bed inpatient facility and could provide essential medical care for U.S. military beneficiaries and others. A joint medical task force joined the support system at the base to aid in the operations. During the course of the outbreak, all crew members underwent testing and evaluation; their well-being was closely monitored, and they were isolated or quarantined, if necessary. Study methodology For this report, the team collected all clinical and medical data from every crew member on board. This included the results of the testing by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). All the crew members were then followed up for at least ten weeks with or without a positive test or presence of symptoms. Start of the outbreak The ship was at sea for 13 days when three of the crew developed symptoms suggestive of COVID-19. They underwent testing with RT-PCR and tested positive. Within 24 hours of this, 400 close contacts of these three and other symptomatic persons were traced. Four days following the first positive results, the ship docked at the Naval Base Guam, and those who tested positive were evacuated from the base or placed in the base hospital in isolation. Others who had no symptoms of COVID-19 and had one or more negative tests were kept in quarantine either at hotels off base or on Naval Base Guam. Uninfected persons and essential crew members remained on board with the ship docked at port. Testing and monitoring For all the crew members in isolation or quarantine, screening for signs and symptoms of the infection was done along with testing. All persons in isolation were checked twice a day for symptoms, temperature and pulse oxygen saturation. Overall, 4,079 SARS-CoV-2–negative crew members were housed in 11 hotels in Guam in quarantine in single rooms. All persons were asked for a self-assessment of symptoms using a symptom checker developed by Defense Digital Service along with health screenings. These data were gathered each morning and evening at 9 AM and 9 PM, respectively. Those that showed worsening symptoms were provided adequate hospitalization and care, and all crew members were provided primary care, pharmacy and psychiatric services. After 14 days, all crew members underwent repeat RT-PCR testing (at the end of the isolation or quarantine period of 14 days). The isolation period ended after a symptom-free three days before exit testing. Those in quarantine with additional symptoms and positive test results were shifted to isolation for at least 14 additional days. All members were followed up for at least ten weeks, even after isolation and quarantine. The Navy and Marine Corps Public Health Center was responsible for providing data collection and analysis support. Results The overall results of the analysis:
- The average age of the crew members was 27 years, with most in general good health that met U.S. Navy standards for sea duty.
- During the outbreak period (between March 23 and May 18, 2020), a total of 1,271 crew members (12.6 percent) tested positive for SARS-CoV-2 by RT-PCR testing
- Most infections occurred within five weeks of the first case detected on board
- 60 crew members did not test positive for COVID-19 but had symptoms similar to the condition meeting the Council of State and Territorial Epidemiologists clinical criteria for COVID-19
- Among those testing positive, 978 of 1,271 (76.9 percent) had no symptoms at diagnosis
- 55 percent (699) of those testing positive developed symptoms during the course of the infection
- A similar spread pattern was seen among men and women on board
- Among 1,331 crew members who had suspected or confirmed COVID-19, 1.7 percent (23) needed hospitalization, 0.3 percent (4) needed intensive care, and one person succumbed to the infection.
- The team wrote, “Although the ship docked in Guam on March 27, 2020, the outbreak continued for at least an additional six weeks”.
- Matthew R. Kasper, Ph.D., Jesse R. Geibe, M.D., Christine L. Sears, M.D., Asha J. Riegodedios, M.S.P.H., Tina Luse, M.P.H., Annette M. Von Thun, M.D., Michael B. McGinnis, M.D., Niels Olson, M.D., Daniel Houskamp, M.D., Robert Fenequito, M.D., Timothy H. Burgess, M.D., Adam W. Armstrong, M.D., et al. An Outbreak of Covid-19 on an Aircraft Carrier. The New England Journal of Medicine. DOI: 10.1056/NEJMoa2019375, https://www.nejm.org/doi/10.1056/NEJMoa2019375