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1.
Lancet Infect Dis ; 22(3): 413-425, 2022 03.
Article in English | MEDLINE | ID: covidwho-1839423

ABSTRACT

BACKGROUND: The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. METHODS: The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16-23 years) or men who have sex with men (MSM; aged 16-26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov, NCT00090285. FINDINGS: Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1-11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0-6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0-8·7) versus 137·3 (83·9-212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0-7·7) versus 140·4 (89·0-210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5-114·4) versus 906·2 (553·5-1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6-212·3] vs 0 cases per 10 000 person-years [0·0-13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0-215·7] vs 0 cases per 10 000 person-years [0·0-10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9-1289·1] vs 101·3 cases per 10 000 person-years [32·9-236·3]). No vaccine-related serious adverse events were reported. INTERPRETATION: The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. FUNDING: Merck Sharp & Dohme.


Subject(s)
Anus Neoplasms , Condylomata Acuminata , Papillomavirus Infections , Papillomavirus Vaccines , Sexual and Gender Minorities , Condylomata Acuminata/epidemiology , Condylomata Acuminata/prevention & control , Double-Blind Method , Follow-Up Studies , Homosexuality, Male , Humans , Immunogenicity, Vaccine , Male , Papillomaviridae , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control
2.
Front Cell Infect Microbiol ; 11: 790422, 2021.
Article in English | MEDLINE | ID: covidwho-1789351

ABSTRACT

Patients with Coronavirus Disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly present with respiratory issues and related symptoms, in addition to significantly affected digestive system, especially the intestinal tract. While several studies have shown changes in the intestinal flora of patients with COVID-19, not much information is available on the gut virome of such patients. In this study, we used the viromescan software on the latest gut virome database to analyze the intestinal DNA virome composition of 15 patients with COVID-19 and investigated the characteristic alternations, particularly of the intestinal DNA virome to further explore the influence of COVID-19 on the human gut. The DNA viruses in the gut of patients with COVID-19 were mainly crAss-like phages (35.48%), Myoviridae (20.91%), and Siphoviridae (20.43%) family of viruses. Compared with healthy controls, the gut virome composition of patients with COVID-19 changed significantly, especially the crAss-like phages family, from the first time of hospital admission. A potential correlation is also indicated between the change in virome and bacteriome (like Tectiviridae and Bacteroidaceae). The abundance of the viral and bacterial population was also analyzed through continuous sample collection from the gut of patients hospitalized due to COVID-19. The gut virome is indeed affected by the SARS-CoV-2 infection, and along with gut bacteriome, it may play an important role in the disease progression of COVID-19. These conclusions would be helpful in understanding the gut-related response and contribute to the treatment and prevention strategies of COVID-19.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , DNA , Humans , SARS-CoV-2 , Virome
3.
EBioMedicine ; 78: 103944, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1778091

ABSTRACT

BACKGROUND: SARS-CoV-2 vaccines currently authorized for emergency use have been highly successful in preventing infection and lessening disease severity. The vaccines maintain effectiveness against earlier SARS-CoV-2 Variants of Concern but the heavily mutated, highly transmissible Omicron variant presents an obstacle both to vaccine protection and monoclonal antibody therapies. METHODS: Pseudotyped lentiviruses were incubated with serum from vaccinated and boosted donors or therapeutic monoclonal antibody and then applied to target cells. After 2 days, luciferase activity was measured in a microplate luminometer. Resistance mutations of the Omicron spike were identified using point-mutated spike protein pseudotypes and mapped onto the three-dimensional spike protein structure. FINDINGS: Virus with the Omicron spike protein was 26-fold resistant to neutralization by recovered donor sera and 26-34-fold resistance to Pfizer BNT162b2 and Moderna vaccine-elicited antibodies following two immunizations. A booster immunization increased neutralizing titres against Omicron. Neutralizing titres against Omicron were increased in the sera with a history of prior SARS-CoV-2 infection. Analysis of the therapeutic monoclonal antibodies showed that the Regeneron and Eli Lilly monoclonal antibodies were ineffective against the Omicron pseudotype while Sotrovimab and Evusheld were partially effective. INTERPRETATION: The results highlight the benefit of a booster immunization to protect against the Omicron variant and demonstrate the challenge to monoclonal antibody therapy. The decrease in neutralizing titres against Omicron suggest that much of the vaccine efficacy may rely on T cells. FUNDING: The work was funded by grants from the NIH to N.R.L. (DA046100, AI122390 and AI120898) and 55 to M.J.M. (UM1AI148574).


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Spike Glycoprotein, Coronavirus/genetics , Vaccination
4.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1762664

ABSTRACT

The increasing prevalence of SARS-CoV-2 variants has raised concerns regarding possible decreases in vaccine effectiveness. Here, neutralizing antibody titers elicited by mRNA-based and adenoviral vector-based vaccines against variant pseudotyped viruses were measured. BNT162b2 and mRNA-1273-elicited antibodies showed modest neutralization resistance against Beta, Delta, Delta plus and Lambda variants whereas Ad26.COV2.S-elicited antibodies from a significant fraction of vaccinated individuals had less neutralizing titer (IC50 <50). The data underscore the importance of surveillance for breakthrough infections that result in severe COVID-19 and suggest a potential benefit by second immunization following Ad26.COV2.S to increase protection from current and future variants.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315713

ABSTRACT

The considerable cessation of human activities during the COVID-19 pandemic has affected global energy use and CO2 emissions. Here we show the unprecedented decrease in global fossil CO2 emissions from January to April 2020 was of 7.8% (938 Mt CO2 with a +6.8% of 2-σ uncertainty) when compared with the period last year. In addition other emerging estimates of COVID impacts based on monthly energy supply or estimated parameters, this study contributes to another step that constructed the near-real-time daily CO2 emission inventories based on activity from power generation (for 29 countries), industry (for 73 countries), road transportation (for 406 cities), aviation and maritime transportation and commercial and residential sectors emissions (for 206 countries). The estimates distinguished the decline of CO2 due to COVID-19 from the daily, weekly and seasonal variations as well as the holiday events. The COVID-related decreases in CO2 emissions in road transportation (340.4 Mt CO2, -15.5%), power (292.5 Mt CO2, -6.4% compared to 2019), industry (136.2 Mt CO2, -4.4%), aviation (92.8 Mt CO2, -28.9%), residential (43.4 Mt CO2, -2.7%), and international shipping (35.9Mt CO2, -15%). Regionally, decreases in China were the largest and earliest (234.5 Mt CO2,-6.9%), followed by Europe (EU-27 & UK) (138.3 Mt CO2, -12.0%) and the U.S. (162.4 Mt CO2, -9.5%). The declines of CO2 are consistent with regional nitrogen oxides concentrations observed by satellites and ground-based networks, but the calculated signal of emissions decreases (about 1Gt CO2) will have little impacts (less than 0.13ppm by April 30, 2020) on the overserved global CO2 concertation. However, with observed fast CO2 recovery in China and partial re-opening globally, our findings suggest the longer-term effects on CO2 emissions are unknown and should be carefully monitored using multiple measures.

6.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327694

ABSTRACT

Monoclonal antibody therapy for the treatment of SARS-CoV-2 infection has been highly successful in decreasing disease severity;however, the recent emergence of the heavily mutated Omicron variant has posed a challenge to this treatment strategy. The Omicron variant BA.1 has been found to evade neutralization by the Regeneron and Eli Lilly therapeutic monoclonal antibodies, while Sotrovimab and the Evusheld monoclonal antibody cocktail retain significant neutralizing activity. A newly emerged variant, Omicron BA.2, containing the BA.1 mutations plus an additional 6 mutations and 3 deletions, 3 of which lie in the receptor binding domain, has been found to be spreading with increased transmissibility. We report here, using a spike protein-pseudotyped lentivirus assay, that Omicron BA.2 is not neutralized with detectable titer by any of the therapeutic monoclonal antibodies, including Sotrovimab and the Evusheld monoclonal antibodies. The results demonstrate the difficulty of identifying broadly neutralizing monoclonal antibodies against SARS-CoV-2 and the importance of the T cell response from which immunoevasion is more difficult.

7.
Cell Rep ; 38(2): 110237, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588138

ABSTRACT

Recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants Mu and C.1.2 have spike proteins with mutations that may confer resistance to natural and vaccine-elicited antibodies. Analysis of neutralizing antibody titers in the sera of vaccinated individuals without previous history of infection and from convalescent individuals show partial resistance of the viruses. In contrast, sera from individuals with a previous history of SARS-CoV-2 infection who were subsequently vaccinated neutralize variants with titers 4- to 11-fold higher, providing a rationale for vaccination of individuals with previous infection. The heavily mutated C.1.2 spike is the most antibody neutralization-resistant spike to date; however, the avidity of C.1.2 spike protein for angiotensin-converting enzyme 2 (ACE2) is low. This finding suggests that the virus evolved to escape the humoral response but has a decrease in fitness, suggesting that it may cause milder disease or be less transmissible. It may be difficult for the spike protein to evolve to escape neutralizing antibodies while maintaining high affinity for ACE2.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , A549 Cells , Cell Line , Cell Line, Tumor , HEK293 Cells , Humans , Neutralization Tests/methods , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods
8.
Frontiers in cellular and infection microbiology ; 11, 2021.
Article in English | EuropePMC | ID: covidwho-1564449

ABSTRACT

Patients with Coronavirus Disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly present with respiratory issues and related symptoms, in addition to significantly affected digestive system, especially the intestinal tract. While several studies have shown changes in the intestinal flora of patients with COVID-19, not much information is available on the gut virome of such patients. In this study, we used the viromescan software on the latest gut virome database to analyze the intestinal DNA virome composition of 15 patients with COVID-19 and investigated the characteristic alternations, particularly of the intestinal DNA virome to further explore the influence of COVID-19 on the human gut. The DNA viruses in the gut of patients with COVID-19 were mainly crAss-like phages (35.48%), Myoviridae (20.91%), and Siphoviridae (20.43%) family of viruses. Compared with healthy controls, the gut virome composition of patients with COVID-19 changed significantly, especially the crAss-like phages family, from the first time of hospital admission. A potential correlation is also indicated between the change in virome and bacteriome (like Tectiviridae and Bacteroidaceae). The abundance of the viral and bacterial population was also analyzed through continuous sample collection from the gut of patients hospitalized due to COVID-19. The gut virome is indeed affected by the SARS-CoV-2 infection, and along with gut bacteriome, it may play an important role in the disease progression of COVID-19. These conclusions would be helpful in understanding the gut-related response and contribute to the treatment and prevention strategies of COVID-19.

9.
Oxid Med Cell Longev ; 2021: 6966394, 2021.
Article in English | MEDLINE | ID: covidwho-1528596

ABSTRACT

Subarachnoid hemorrhage (SAH) is a cerebrovascular disease associated with high morbidity and mortality. CXCR4 provides neuroprotective effects, which can alleviate brain injury and inflammation induced by stroke. Previous studies have suggested that CXCR4 reduces the pyroptosis of LPS-stimulated BV2 cells. The purpose of this study was to evaluate the antipyroptosis effects and mechanisms of CXCR4 after SAH. SAH animal model was induced via endovascular perforation. A total of 136 male Sprague-Dawley rats were used. Recombinant human cysteine-X-cysteine chemokine ligand 12 (rh-CXCL-12) was administered intranasally at 1 h after SAH induction. To investigate the underlying mechanism, the inhibitor of CXCR4, AMD3100, was administered intraperitoneally at 1 h before SAH. The neurobehavior tests were assessed, followed by performing Western blot and immunofluorescence staining. The Western blot results suggested that the expressions of endogenous CXCL-12, CXCR4, and NLRP1 were increased and peaked at 24 h following SAH. Immunofluorescence staining showed that CXCR4 was expressed on neurons, microglia, and astrocytes. Rh-CXCL-12 treatment improved the neurological deficits and reduced the number of FJC-positive cells, IL-18-positive neurons, and cleaved caspase-1(CC-1)-positive neurons after SAH. Meanwhile, rh-CXCL-12 treatment increased the levels of CXCL-12 and CXCR4, and reduced the levels of NLRP1, IL-18, IL-1ß, and CC-1. Moreover, the administration of AMD3100 abolished antipyroptosis effects of CXCL-12 and its regulation of CXCR4 post-SAH. The CXCR4/NLRP1 signaling pathway may be involved in CXCL-12-mediated neuronal pyroptosis after SAH. Early administration of CXCL-12 may be a preventive and therapeutic strategy against brain injury after SAH.


Subject(s)
Brain Injuries/prevention & control , Chemokine CXCL12/administration & dosage , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Pyroptosis , Receptors, CXCR4/metabolism , Subarachnoid Hemorrhage/complications , Animals , Brain Injuries/etiology , Brain Injuries/metabolism , Brain Injuries/pathology , Chemokine CXCL12/metabolism , Disease Models, Animal , Gene Expression Regulation , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Inflammation/prevention & control , Male , Nerve Tissue Proteins/genetics , Neurons/pathology , Rats , Rats, Sprague-Dawley , Receptors, CXCR4/genetics , Signal Transduction
10.
iScience ; 24(11): 103341, 2021 Nov 19.
Article in English | MEDLINE | ID: covidwho-1474648

ABSTRACT

Highly transmissible SARS-CoV-2 variants identified in India and designated B.1.617, Kappa (B.1.617.1), Delta (B.1.617.2), B.1.618, and B.1.36.29 contain spike mutations L452R, T478K, E484K, E484Q, and N440K located within the spike receptor-binding domain and thus could contribute to increased transmissibility and potentially allow re-infection or cause resistance to vaccine-elicited antibody. To address these issues, we used lentiviruses pseudotyped by variant spikes to measure their neutralization by convalescent sera, vaccine-elicited and Regeneron therapeutic antibodies, and ACE2 affinity. Convalescent sera and vaccine-elicited antibodies neutralized viruses with Delta spike with 2- to 5-fold decrease in titer in different donors. Regeneron antibody cocktail neutralized virus with the Delta spike with a 2.6-fold decrease in titer. Neutralization resistance to serum antibodies and monoclonal antibodies was mediated by L452R mutation. These relatively modest decreases in antibody neutralization titer for viruses with variant spike proteins suggest that current vaccines will remain protective against the family of Delta variants.

11.
mBio ; 12(4): e0138621, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1327615

ABSTRACT

DNA sequence analysis recently identified the novel SARS-CoV-2 variant B.1.526 that is spreading at an alarming rate in the New York City area. Two versions of the variant were identified, both with the prevalent D614G mutation in the spike protein, together with four novel point mutations and with an E484K or S477N mutation in the receptor-binding domain, raising concerns of possible resistance to vaccine-elicited and therapeutic antibodies. We report that convalescent-phase sera and vaccine-elicited antibodies retain full neutralizing titer against the S477N B.1.526 variant and neutralize the E484K version with a modest 3.5-fold decrease in titer compared to D614G. The E484K version was neutralized with a 12-fold decrease in titer by the REGN10933 monoclonal antibody, but the combination cocktail with REGN10987 was fully active. The findings suggest that current vaccines and Regeneron therapeutic monoclonal antibodies will remain protective against the B.1.526 variants. The findings further support the value of widespread vaccination. IMPORTANCE A novel SARS-CoV-2 variant termed B.1.526 was recently identified in New York City and has been found to be spreading at an alarming rate. The variant has mutations in its spike protein that might allow it to escape neutralization by vaccine-elicited antibodies and might cause monoclonal antibody therapy for COVID-19 to be less successful. We report here that these fears are not substantiated; convalescent-phase sera and vaccine-elicited antibodies neutralized the B.1.526 variant. One of the Regeneron therapeutic monoclonal antibodies was less effective against the B.1.526 (E484K) variant but the two-antibody combination cocktail was fully active. The findings should assuage concerns that current vaccines will be ineffective against the B.1.526 (E484K) variant and suggest the importance of continued widespread vaccination.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Cell Line , HEK293 Cells , Humans , New York City , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccination
12.
China CDC Wkly ; 3(32): 681-687, 2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1296414

ABSTRACT

What is already known about this topic? The coronavirus disease 2019 (COVID-19) epidemic in China had been effectively controlled for several months, but as the ambient temperature dropped, large gathering-initiated epidemics occurred in northern China, including Hebei, Liaoning, and Jilin provinces. What is added by this report? A sudden epidemic emerged in Wangkui County, Suihua City, Heilongjiang Province, on January 9, 2021. An asymptomatically-infected resident of Harbin City returned from Suihua and triggered a large-scale outbreak in the Zhengda Food Processing Company in Harbin, Heilongjiang. The epidemic was associated with widespread community transmission inside and outside the company, eventually leading to 260 persons being infected (87.8% of 296 patients in Harbin). What are the implications for public health practice? This study demonstrates the importance of screening for infections in the COVID-19 prevention and control system, shares experiences identifying and managing asymptomatic infections, and recommends food processing enterprises like the Zhengda Company to improve preventative measures. Our evidence-based epidemiological analyses provide methods for finding high-risk settings and evaluating epidemic situations when many asymptomatic patients are identified in a short period of time.

13.
Indoor Air ; 31(6): 1833-1842, 2021 11.
Article in English | MEDLINE | ID: covidwho-1285031

ABSTRACT

Since the coronavirus disease 2019 (COVID-19) outbreak, the nosocomial infection rate worldwide has been reported high. It is urgent to figure out an affordable way to monitor and alarm nosocomial infection. Carbon dioxide (CO2 ) concentration can reflect the ventilation performance and crowdedness, so CO2 sensors were placed in Beijing Tsinghua Changgung Hospital's fever clinic and emergency department where the nosocomial infection risk was high. Patients' medical records were extracted to figure out their timelines and whereabouts. Based on these, site-specific CO2 concentration thresholds were calculated by the dilution equation and sites' risk ratios were determined to evaluate ventilation performance. CO2 concentration successfully revealed that the expiratory tracer was poorly diluted in the mechanically ventilated inner spaces, compared to naturally ventilated outer spaces, among all of the monitoring sites that COVID-19 patients visited. Sufficient ventilation, personal protection, and disinfection measures led to no nosocomial infection in this hospital. The actual outdoor airflow rate per person (Qc ) during the COVID-19 patients' presence was estimated for reference using equilibrium analysis. During the stay of single COVID-19 patient wearing a mask, the minimum Qc value was 15-18 L/(s·person). When the patient was given throat swab sampling, the minimum Qc value was 21 L/(s·person). The Qc value reached 36-42 L/(s·person) thanks to window-inducted natural ventilation, when two COVID-19 patients wearing masks shared the same space with other patients or healthcare workers. The CO2 concentration monitoring system proved to be effective in assessing nosocomial infection risk by reflecting real-time dilution of patients' exhalation.


Subject(s)
Air Pollution, Indoor , COVID-19 , Cross Infection , Air Microbiology , Air Pollution, Indoor/analysis , COVID-19/prevention & control , Cross Infection/prevention & control , Hospitals , Humans , SARS-CoV-2 , Ventilation
14.
mBio ; 12(3): e0069621, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1249476

ABSTRACT

The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations raises concerns that antibodies elicited by natural infection or vaccination and therapeutic monoclonal antibodies will become less effective. We show that convalescent-phase sera neutralize pseudotyped viruses with the B.1.1.7, B.1.351, B.1.1.248, COH.20G/677H, 20A.EU2, and mink cluster 5 spike proteins with only a minor loss in titer. Similarly, antibodies elicited by Pfizer BNT162b2 vaccination neutralized B.1.351 and B.1.1.248 with only a 3-fold decrease in titer, an effect attributable to E484K. Analysis of the Regeneron monoclonal antibodies REGN10933 and REGN10987 showed that REGN10933 has lost neutralizing activity against the B.1.351 and B.1.1.248 pseudotyped viruses, and the cocktail is 9- to 15-fold decreased in titer. These findings suggest that antibodies elicited by natural infection and by the Pfizer vaccine will maintain protection against the B.1.1.7, B.1.351, and B.1.1.248 variants but that monoclonal antibody therapy may be less effective for patients infected with B.1.351 or B.1.1.248 SARS-CoV-2. IMPORTANCE The rapid evolution of SARS-CoV-2 variants has raised concerns with regard to their potential to escape from vaccine-elicited antibodies and anti-spike protein monoclonal antibodies. We report here on an analysis of sera from recovered patients and vaccinated individuals and on neutralization by Regeneron therapeutic monoclonal antibodies. Overall, the variants were neutralized nearly as well as the wild-type pseudotyped virus. The B.1.351 variant was somewhat resistant to vaccine-elicited antibodies but was still readily neutralized. One of the two Regeneron therapeutic monoclonal antibodies seems to have lost most of its activity against the B.1.351 variant, raising concerns that the combination therapy might be less effective for some patients. The findings should alleviate concerns that vaccines will become ineffective but suggest the importance of continued surveillance for potential new variants.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , COVID-19/therapy , Cell Line , HEK293 Cells , Humans , Immunization, Passive , Spike Glycoprotein, Coronavirus/immunology , Vaccination
15.
J Cancer ; 12(8): 2450-2455, 2021.
Article in English | MEDLINE | ID: covidwho-1148349

ABSTRACT

Chemotherapy is the major method of treatment for acute leukemia to date, while intensive chemotherapy may impair immunity. We previously reported that leukemia patients were more susceptible to COVID-19 than the overall population. However, for COVID-19 recovered patients with leukemia, the impacts of intensive chemotherapy on the immune memory of COVID-19 are unknown. This study characterized the changes in immune cells and SARS-CoV-2 antibodies in acute leukemia patients, who underwent chemotherapy after recovering from COVID-19. The study enrolled three groups of individuals. One group was a total of three acute leukemia patients, who recovered well from COVID-19 before the last cycle of chemotherapy. The other two groups were six COVID-19 recovered healthy people, and six normal uninfected healthy people, respectively. Levels of B cells, T cells, and NK cells in peripheral blood were analyzed by multiparameter flow cytometry. Besides, the SARS-CoV-2 antibodies were monitored. The results showed that B cells were severely decreased after chemotherapy, especially memory B cells. Most of the T cells and NK cells showed only minor changes after chemotherapy, except for γδ T cells. The serum levels of SARS-CoV-2 antibodies were not significantly affected after chemotherapy in two leukemia patients. However, interestingly, one leukemia patient's SARS-CoV-2 IgM showed dramatically increase, suggesting possible loss of serological memory after chemotherapy. These findings raised the concern for the stability of immune memory against SARS-CoV-2 during chemotherapy and the choice of anti-leukemia treatment in the COVID-19 pandemic.

16.
Front Genet ; 12: 641445, 2021.
Article in English | MEDLINE | ID: covidwho-1133907

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription of SARS-CoV-2 has recently emerged, their regulation remains unknown. RESULTS: By comprehensive analysis of genome sequence and protein structure data, we propose a negative feedback model to explain the regulation of CoV replication and transcription, providing a molecular basis of the "leader-to-body fusion" model. The key step leading to the proposal of our model was that the transcription regulatory sequence (TRS) motifs were identified as the cleavage sites of nsp15, a nidoviral RNA uridylate-specific endoribonuclease (NendoU). According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs), and genomic RNAs (gRNAs) by cleaving TRSs. The expression level of nsp15 controls the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nsp15 to reach equilibrium between the CoV replication and transcription. CONCLUSION: The replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g., uridine derivatives) against CoVs.

17.
Exp Ther Med ; 21(4): 392, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1119577

ABSTRACT

A continuing outbreak of pneumonia associated with the 2019 novel coronavirus (2019-nCoV) was initially described in Wuhan, China in December 2019. Weak and elderly individuals, and those with chronic diseases such as hematological malignancies are prone to develop severe pneumonia. The humoral immunity of patients with multiple myeloma is prevalently low, and their inferior immunity further deteriorates during chemotherapy. For patients with onco-hematological malignancies infected with 2019-nCoV during the first chemotherapy cycle, the clinical treatment experience is lacking. The present study is a report of a 61-year-old patient newly diagnosed with multiple myeloma in the key 2019-nCoV outbreak area, who suffered severe 2019-nCoV pneumonia during the first chemotherapy cycle. The present case report demonstrated that a rapidly progressive and severe form of pneumonia was a specific clinical feature of COVID-19, especially in immunocompromised patients with cancer. The treatment strategy combining timely suspending chemotherapy, early intervention using intravenous immunoglobulin, interferon α inhalation and oral antiviral drugs was effective. Therefore, in the pandemic environment, it is strongly recommend that the risk of 2019-nCoV infection is assessed prior to chemotherapy.

19.
Nat Commun ; 11(1): 5172, 2020 10 14.
Article in English | MEDLINE | ID: covidwho-963670

ABSTRACT

The COVID-19 pandemic is impacting human activities, and in turn energy use and carbon dioxide (CO2) emissions. Here we present daily estimates of country-level CO2 emissions for different sectors based on near-real-time activity data. The key result is an abrupt 8.8% decrease in global CO2 emissions (-1551 Mt CO2) in the first half of 2020 compared to the same period in 2019. The magnitude of this decrease is larger than during previous economic downturns or World War II. The timing of emissions decreases corresponds to lockdown measures in each country. By July 1st, the pandemic's effects on global emissions diminished as lockdown restrictions relaxed and some economic activities restarted, especially in China and several European countries, but substantial differences persist between countries, with continuing emission declines in the U.S. where coronavirus cases are still increasing substantially.


Subject(s)
Air Pollutants/analysis , Carbon Dioxide/analysis , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Air Pollutants/economics , Betacoronavirus , COVID-19 , Carbon Dioxide/economics , Coronavirus Infections/economics , Coronavirus Infections/prevention & control , Environmental Monitoring , Fossil Fuels/analysis , Fossil Fuels/economics , Humans , Industry/economics , Nitrogen Dioxide/analysis , Nitrogen Dioxide/economics , Pandemics/economics , Pandemics/prevention & control , Pneumonia, Viral/economics , Pneumonia, Viral/prevention & control , SARS-CoV-2
20.
J Med Virol ; 92(10): 1980-1987, 2020 10.
Article in English | MEDLINE | ID: covidwho-935087

ABSTRACT

The coronavirus disease 2019 (COVID-19) outbroke in Wuhan, Hubei Province, China, affecting more than 200 countries and regions. This study aimed to predict the development of the epidemic with specific interventional policies applied in China and evaluate their effectiveness. COVID-19 data of Hubei Province and the next five most affected provinces were collected from daily case reports of COVID-19 on the Health Committee official website of these provinces. The number of current cases, defined as the number of confirmed cases minus the number of cured cases and those who have died, were examined in this study. A modified susceptible-exposed-infectious-removed (SEIR) model was used to assess the effects of interventional policies on the epidemic. In this study, 28 January was day 0 of the model. The results of the modified SEIR model showed that the number of current cases in Hubei and Zhejiang provinces tended to be stabilized after 70 days and after 60 days in the four other provinces. The predicted number of current cases without policy intervention was shown to far exceed that with policy intervention. The estimated number of COVID-19 cases in Hubei Province with policy intervention was predicted to peak at 51 222, whereas that without policy intervention was predicted to reach 157 721. Based on the results of the model, strong interventional policies were found to be vital components of epidemic control. Applying such policies is likely to shorten the duration of the epidemic and reduce the number of new cases.


Subject(s)
COVID-19/prevention & control , Communicable Disease Control/legislation & jurisprudence , Health Policy , Pandemics/prevention & control , China , Forecasting , Humans , Models, Theoretical
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