Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
1.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327123

ABSTRACT

Since the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325079

ABSTRACT

Ten emerging SARS-CoV-2 variants—B.1.1.298, B.1.1.7, B.1.351, P.1, P.2, B.1.429, B.1.525, B.1.526-1, B.1.526-2, B.1.1.318—and seven corresponding single amino acid mutations in the receptor-binding domain were examined using SARS-CoV-2 pseudovirus. The results indicate that the current SARS-CoV-2 variants do not increase infectivity among humans. The K417N/T, N501Y, or E484K-carrying variants exhibited increased abilities to infect to mouse ACE2-overexpressing cells. The activities of Furin, TMPRSS2, and cathepsin L were increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y caused significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines was mainly caused by the E484K mutation, while the neutralization of E484K-carrying variants was decreased by 1.1–6.2-fold. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322743

ABSTRACT

Background: Towards the end of December 2019, the Wuhan health commission declared an outbreak of clusters of pneumonia in patients. Sequencing indicated that this disease (COVID-19) was caused by a novel coronavirus (SARS-CoV-2). The outbreak of COVID-19 is currently still underway. Methods We recruited 75 SARS-CoV-2 infected patients admitted to the Center of Infectious Disease division 2 of Beijing Ditan Hospital from Jan 20 to Mar 20, 2020. Epidemiological, demographic, clinical, radiological features, laboratory data were analyzed. Results Of the 75 patients, 42(56%) patients were male and 33(44%) patients were female. The mean age of all patients was 41.5 ± 19.4 years. Male patients were more likely to become severe. There were 9 family clusters accounted for 44 patients. Patients classified as being severe had a higher frequency of fever upon admission than patients classified as moderate cases. For moderate patients, the median duration of viral shedding was 25(9.5, 42) days (range 1–63 days) from the first positive nucleic acid test compared to 14(9, 21.25) days (range 2–62 days) for severe cases. The difference between the two groups was statistically significant (p = 0.041). Cox regression analyses indicated that disease status and CRP were the factors that affect the duration of viral shedding. Virus clearance was significantly faster in severe patients compared to moderate patients(p = 0.011), and patients with CRP range in 2–10 times higher than upper limit of normal value had longer duration of viral shedding(p = 0.012). CRP and CD4 + T lymphocyte was negative correlated, and the relationship between CRP and CD4 + T lymphocyte was statistically significant (P = 0.003), with a correlation coefficient of -0.564. During the second week following the onset of illness, severe cases had higher WBC, NEU and CRP, but lower LYM, MON and EOS as compared with moderate cases (all P < 0.05). Severe cases still had lower lymphocyte counts and higher CRP than moderate cases in the third week. Conclusions Viral clearance was significantly prolonged in moderate patients, and those CRP in 2–10 times higher than upper limit of normal value. Immune response may affect the duration of viral shedding. Severe cases had a persistence lower lymphocyte count and higher CRP than moderate cases.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315601

ABSTRACT

Background: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people’s attentions. Whether interferon alfa-2b or Kaletra plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown. Methods: : This is a retrospective cohort study of 123 laboratory-confirmed COVID-19 patients between Jan.13 2020 and Apr. 23. All patients received standard supportive care and regular clinical monitoring , patients were assigned to standard care group (n=12), interferon alfa-2b group (n=44), and combination Kaletra plus interferon alfa-2b group (n=67) according to their therapies. The primary endpoint for this study was the duration of oxygen-support requirement and virus clearance time. The associations of therapies with these outcomes were assessed by Cox proportional hazards regression. Results: : Baseline clinical and laboratory characteristics were similar among 3 groups (p>0.05). There was no significant association of Kaletra /interferon alfa-2b with faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% CI, 0.45–1.61];P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI, 0.32–1.11];P = 0.10 in Kaletra plus interferon alfa-2b group). The duration of oxygen-support requirement in therapy groups similarly showed no significant association. There were no differences among 3 groups in the incidence of adverse events (p>0.05). Conclusions: : In patients with confirmed SARS-CoV-2 infection, no benefit was observed with interferon alfa-2b and Kaletra plus interferon alfa-2b treatment beyond standard care. Further trials in appropriately randomized design may contribute to validate the effective role and safety profile of the test drugs.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315201

ABSTRACT

The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.

6.
J Med Virol ; 94(5): 2237-2249, 2022 May.
Article in English | MEDLINE | ID: covidwho-1664417

ABSTRACT

As the coronavirus disease 2019 (COVID-19) pandemic is still ongoing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are circulating worldwide, an increasing number of breakthrough infections are being detected despite the good efficacy of COVID-19 vaccines. Data on 88 COVID-19 breakthrough cases (breakthrough infections group) and 41 unvaccinated cases (unvaccinated group) from June 1 to August 22, 2021, were extracted from a cloud database established at Beijing Ditan Hospital to evaluate the clinical, immunological, and genomic characteristics of COVID-19 breakthrough infections. Among these 129 COVID-19 cases, 33 whole genomes were successfully sequenced, of which 23 were Delta variants, including 15 from the breakthrough infections group. Asymptomatic and mild cases predominated in both groups, but two patients developed severe disease in the unvaccinated group. The median time of viral shedding in the breakthrough infections group was significantly lower than that in the unvaccinated group (p = 0.003). In the breakthrough infections group, the IgG titers showed a significantly increasing trend (p = 0.007), and the CD4 + T lymphocyte count was significantly elevated (p = 0.018). For people infected with the Delta variant in the two groups, no significant difference was observed in either the quantitative reverse-transcription polymerase chain reaction results or viral shedding time. In conclusion, among vaccinated patients, the cases of COVID-19 vaccine breakthrough infections were mainly asymptomatic and mild, IgG titers were significantly increased and rose rapidly, and the viral shedding time was shorter.


Subject(s)
COVID-19 , Beijing/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Genomics , Humans , SARS-CoV-2/genetics
8.
Cell Rep ; 38(2): 110205, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588142

ABSTRACT

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.


Subject(s)
COVID-19/virology , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/genetics , Young Adult
9.
Commun Biol ; 4(1): 1196, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1467140

ABSTRACT

Emerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. Here we investigate the infectivity and antigenicity of ten emerging SARS-CoV-2 variants-B.1.1.298, B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), P.2(Zeta), B.1.429(Epsilon), B.1.525(Eta), B.1.526-1(Iota), B.1.526-2(Iota), B.1.1.318-and seven corresponding single amino acid mutations in the receptor-binding domain using SARS-CoV-2 pseudovirus. The results indicate that the pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants. Our study provides insights regarding therapeutic antibodies and vaccines, and highlights the importance of E484K mutation.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/therapy , Cell Line , HEK293 Cells , Humans , Immunization, Passive/methods , Mammals/immunology , Mice , Mutation , Pandemics , Primates/immunology , Protein Binding , Tropism/genetics
10.
BMC Infect Dis ; 21(1): 885, 2021 Aug 30.
Article in English | MEDLINE | ID: covidwho-1379783

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people's attentions. Whether interferon alfa-2b or lopinavir/ritonavir (LPV/r) plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown. The objectives of this study was to evaluate the efficacy and safety of interferon alfa-2b and LPV/r plus interferon alfa-2b for SARS-CoV-2 infection in adult patients hospitalized with COVID-19. METHODS: This is a retrospective cohort study of 123 patients confirmed SARS-CoV-2 infection by PCR on nasopharyngeal swab and symptoms between Jan. 13 and Apr. 23, 2020. All patients received standard supportive care and regular clinical monitoring. Patients were assigned to standard care group (n = 12), interferon alfa-2b group (n = 44), and combination LPV/r plus interferon alfa-2b group (n = 67). The primary endpoints were duration of required oxygen support and virus clearance time. Associations between therapies and these outcomes were assessed by Cox proportional hazards regression. RESULTS: Baseline clinical characteristics were not significantly different among the three groups (P > 0.05). No significant associations were observed between LPV/r/interferon alfa-2b and faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% confidence interval (CI) 0.45-1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI 0.32-1.11]; P = 0.10 in LPV/r plus interferon alfa-2b group). Individual therapy groups also showed no significant association with duration of required oxygen support. There were no significant differences among the three groups in the incidence of adverse events (P > 0.05). CONCLUSIONS: In patients with confirmed SARS-CoV-2 infection, no benefit was observed from interferon alfa-2b or LPV/r plus interferon alfa-2b treatment. The findings may provide references for treatment guidelines of patients with SARS-CoV-2 infection.


Subject(s)
COVID-19 , Ritonavir , Adult , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Combinations , Humans , Interferon alpha-2 , Lopinavir/therapeutic use , RNA, Viral , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2
11.
Microbiol Spectr ; 9(1): e0027321, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1341310

ABSTRACT

The SARS-CoV-2 B.1.1.7 variant has increased sharply in numbers worldwide and is reported to be more contagious than the nonvariant. Little is known regarding the detailed clinical features of B.1.1.7 variant infection. Data on 74 COVID-19 cases from two outbreaks in two districts of Beijing, China were extracted from a cloud database, including 41 cases from Shunyi District (Shunyi B.1.470 group) and 33 from Daxing (Daxing B.1.1.7 group) from December 25, 2020 to January 17, 2021. We conducted a comparison of the clinical characteristics. Seven clinical indicators of the Daxing B.1.1.7 group were significantly higher than those of the Shunyi group, including the proportion with fever over 38°C, the levels of C-reactive protein (CRP), serum amyloid A (SAA), creatine kinase (CK), d-dimer (DD), and CD4+ T lymphocytes (CD4+ T), and the proportion with ground-glass opacity (GGO) in the lung (P values of ≤0.05). After adjusting for age, B.1.1.7 variant infection was a risk factor for elevated CRP (P = 0·045), SAA (P = 0·011), CK (P = 0·034), and CD4+ T (P = 0.029) and for the presence of GGO (P = 0.005). The median threshold cycle (CT) value of reverse transcriptase quantitative PCR (RT-qPCR) tests of the N gene target in the Daxing B.1.1.7 group was significantly lower (P = 0.036) than that in the Shunyi B.1.470 group. Clinical features, including a more serious inflammatory response, pneumonia, and a possibly higher viral load, were detected in the cases infected with B.1.1.7 SARS-CoV-2. The B.1.1.7 variant may have increased pathogenicity. IMPORTANCE The SARS-CoV-2 B.1.1.7 variant, which was first identified in the United Kingdom, has increased sharply in numbers worldwide and was reported to be more contagious than the nonvariant. To our knowledge, no studies investigating the detailed clinical features of COVID-19 cases infected with the B.1.1.7 variant have been published. Local epidemics have rarely occurred in China, but occasionally, a small clustered outbreak triggered by an imported SARS-CoV-2 strain with only one chain of transmission could happen. From late 2020 to early 2021, two clustered COVID-19 outbreaks occurred in Beijing, one of which was caused by the B.1.1.7 variant. The COVID-19 patients from the two outbreaks received similar clinical tests, diagnoses, and treatments. We found that the B.1.1.7 variant infection could lead to a more serious inflammatory response, acute response process, more severe pneumonia, and probably higher viral loads. This therefore implies that the B.1.1.7 variant may have increased pathogenicity.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , SARS-CoV-2/classification , SARS-CoV-2/genetics , Adult , CD4-Positive T-Lymphocytes , China/epidemiology , Cohort Studies , Female , Humans , Lung/virology , Male , Middle Aged , Prospective Studies , Risk Factors , Viral Load , Whole Genome Sequencing
12.
Int J Immunopathol Pharmacol ; 35: 20587384211027679, 2021.
Article in English | MEDLINE | ID: covidwho-1286804

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020. Since then, several studies have found COVID-19 patients with recurrent viral polymerase chain reaction (PCR) positivity. METHODS: On May 6, 2021, an exhaustive literature search of the Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure databases, Embase, Wan Fang Data, VIP database, Sinomed database, BioRxiv, MedRxiv, and Research Square was conducted to find describing the laboratory indicators of recurrent and non-recurrent viral PCR positivity in patients with COVID-19. The data were statistically analyzed using STATA version 15.0. RESULTS: In total, 22 studies-comprising 5154 laboratory-confirmed COVID-19 cases-were included in the analyses. Patients with less severe COVID-19 illness (i.e. those clinically classified as mild or common-type) seemed to exhibit recurrent PCR positivity more commonly than patients with more severe illness (i.e. those classified as severe or critical). There were also significant differences between the two groups in terms of the rates of headaches and dizziness, in addition to the levels of aspartate aminotransferase, C reactive protein, interleukin-6, and lactate dehydrogenase. Further, there were variations in the ratio of CD4+ T cells/CD8+ T cells on admission to the hospital. CONCLUSION: In comparison to COVID-19 patients with non-recurrent viral PCR positivity, patients with recurrent virus PCR positivity seem to experience more severe immune function suppression upon hospital admission.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/immunology , Immunity, Cellular/immunology , Polymerase Chain Reaction/methods , COVID-19/epidemiology , COVID-19 Testing/trends , Humans , Polymerase Chain Reaction/trends , Recurrence
13.
Cell ; 184(13): 3438-3451.e10, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1275185

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Binding Sites/physiology , COVID-19/metabolism , Chiroptera/virology , SARS-CoV-2/pathogenicity , Amino Acid Sequence , Animals , Antibodies, Monoclonal/immunology , COVID-19/immunology , Chiroptera/immunology , Chiroptera/metabolism , Host Specificity/immunology , Humans , Phylogeny , Protein Binding/physiology , Receptors, Virus/metabolism , SARS-CoV-2/immunology , Sequence Alignment
14.
Natl Sci Rev ; 8(4): nwab006, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1254806

ABSTRACT

After a short recovery period, COVID-19 reinfections could occur in convalescent patients, even those with measurable levels of neutralizing antibodies. Effective vaccinations and protective public health measures are recommended for the convalescent COVID-19 patients.

15.
J Acquir Immune Defic Syndr ; 85(2): 239-243, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1165586

ABSTRACT

BACKGROUND: The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified. METHODS: We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared. RESULTS: Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups. CONCLUSIONS: Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.


Subject(s)
Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Antimalarials/therapeutic use , COVID-19 , Chronic Disease , Coronavirus Infections/complications , Drug Combinations , Female , Fever , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Retrospective Studies , Treatment Outcome , Young Adult
16.
Lancet Infect Dis ; 21(8): 1107-1119, 2021 08.
Article in English | MEDLINE | ID: covidwho-1155669

ABSTRACT

BACKGROUND: Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study. METHODS: We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18-59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 µg or 50 µg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 µg or 50 µg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov (NCT04445194 and NCT04466085) and participant follow-up is ongoing. FINDINGS: Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 µg vaccine (n=20), or the 50 µg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 µg vaccine (n=150), or 50 µg vaccine (n=150), or three doses of placebo (n=150), 25 µg vaccine (n=150), or 50 µg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 µg group, and 18 [90%] of 20 in the 50 µg group; phase 2: 37 [25%] of 150 in the two-dose placebo group, 43 [29%] of 150 in the two-dose 25 µg group, 50 [33%] of 150 in the two-dose 50 µg group, 47 [31%] of 150 in the three-dose placebo group, 72 [48%] of 150 in the three-dose 25 µg group, and 65 [43%] of 150 in the three-dose 50 µg group). In phase 1, two (10%) grade 3 or worse adverse events were reported in the 50 µg group. In phase 2, grade 3 or worse adverse events were reported by 18 participants (four [3%] in the two-dose 25 µg vaccine group, two [1%] in the two-dose 50 µg vaccine group, two [1%] in the three-dose placebo group, four [3%] in the three-dose 25 µg vaccine group, and six [4%] in the three-dose 50 µg vaccine group), and 11 were considered vaccine related (two [1%] in the two-dose 25 µg vaccine group, one [1%] in the two-dose 50 µg vaccine group, one [1%] in the three-dose placebo group, two [1%] in the three-dose 25 µg vaccine group, and five [3%] in the three-dose 50 µg vaccine group); seven participants reported serious adverse events (one [1%] in the two-dose 25 µg vaccine group, one [1%] in the two-dose 50 µg vaccine group, two [1%] in the three-dose placebo group, one [1%] in the three-dose 25 µg vaccine group, and two [1%] in the three-dose 50 µg vaccine group), but none was considered vaccine related. In phase 2, on the two-dose schedule, seroconversion rates of neutralising antibodies 14 days after the second dose were 76% (114 of 150 participants) in the 25 µg group and 72% (108 of 150) in the 50 µg group; on the three-dose schedule, seroconversion rates of neutralising antibodies 14 days after the third dose were 97% (143 of 148 participants) in the 25 µg group and 93% (138 of 148) in the 50 µg group. In the two-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the second dose were 17·7 (95% CI 13·6-23·1) in the 25 µg group and 14·1 (10·8-18·3) in the 50 µg group. In the three-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the third dose were 102·5 (95% CI 81·8-128·5) in the 25 µg group and 69·1 (53·0-90·0) in the 50 µg group. INTERPRETATION: The protein subunit vaccine ZF2001 appears to be well tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support the use of the 25 µg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy. FUNDING: National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Antibodies, Viral/blood , COVID-19 Vaccines/adverse effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Protein Multimerization , Tandem Repeat Sequences , Vaccination/adverse effects , Vaccines, Subunit/immunology , Vaccines, Synthetic/immunology
17.
Front Pharmacol ; 11: 634266, 2020.
Article in English | MEDLINE | ID: covidwho-1110322

ABSTRACT

Background: Yindan Jiedu Granules (YDJDG) have been newly prescribed as a Chinese herbal formula. This study aimed to compare the efficacy of YDJDG and lopinavir-ritonavir in the treatment of coronavirus disease 2019 (COVID-19). Methods: Overall, 131 patients with COVID-19 were included in this study. In addition to standard care, 60 of these patients received YDJDG (YDJDG group) and 71 received lopinavir-ritonavir (lopinavir-ritonavir group). Propensity score matching (PSM) was used to match the characteristics of individuals in the two groups, while the Kaplan-Meier method was used to compare the proportion recovery observed. Results: Cox analysis revealed that YDJDG and CD4 ≥ 660 cells/µL were independent predictive factors of proportion recovery. At baseline, disease types differed between the YDJDG and lopinavir-ritonavir treatment groups. Furthermore, no significant adverse effects or toxicities relevant to YDJDG were observed. The median recovery time was 21 days in the YDJDG group and 27 days in the lopinavir-ritonavir group. After PSM (1:1), 50 patient pairs, YDJDG vs. lopinavir-ritonavir, were analyzed. In the YDJDG group, the proportion of recovered patients was remarkably higher than that observed in the lopinavir-ritonavir group (p = 0.0013), especially for those presenting mild/moderate disease type and CD4 < 660 cells/µL. In the YDJDG group, the mean duration of fever and pulmonary exudative lesions was significantly shorter than that observed in the lopinavir-ritonavir group (p = 0.0180 and p = 0.0028, respectively). Conclusion: YDJDG reveals the potential to hasten the recovery period in COVID-19 patients with mild/moderate disease type or CD4 < 660 cells/µL by shortening the mean duration of fever and pulmonary exudative lesions.

18.
J Infect Public Health ; 14(5): 620-627, 2021 May.
Article in English | MEDLINE | ID: covidwho-1074829

ABSTRACT

INTRODUCTION: Many individuals test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA after recovering from the coronavirus disease (COVID-19), but the incidence of reactivation is unknown. We, therefore, estimated the incidence of reactivation among individuals who had recovered from COVID-19 and determined its predictors. METHODS: In this retrospective cohort study, patients with COVID-19 were followed up for at least 14 days after two consecutive negative SARS-CoV-2 polymerase chain reaction test results obtained ≥24 h apart, and the frequency of SARS-CoV-2 reactivation was assessed. RESULTS: Of the 109 patients, 29 (27%) experienced reactivation, and seven (24%) of these were symptomatic. The mean period for the real-time PCR tests for SARS-CoV-2 from negative to positive results was 17 days. Compared with patients without reactivation, those with reactivation were significantly younger and more likely to have a lymphocyte count of <1500/µL (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.12-0.94) and two or fewer symptoms (OR: 0.20, 95% CI: 0.07-0.55) during the initial episode. CONCLUSION: Risk-stratified surveillance should be conducted among patients who have recovered from COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Real-Time Polymerase Chain Reaction , Retrospective Studies
19.
J Med Virol ; 93(5): 3033-3046, 2021 May.
Article in English | MEDLINE | ID: covidwho-1062111

ABSTRACT

We primarily quantified exposure patterns, transmission characteristics, and the clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among household contacts of individuals with severe coronavirus disease-2019 (COVID-19). We conducted a retrospective cohort study of 20 index patients hospitalized with severe COVID-19 and 79 of their household contacts. We determined the transmission frequency, range of manifestations of SARS-CoV-2 infection, and factors associated with infection in household settings. Of the 79 household contacts, 53 (67%) developed SARS-CoV-2 infection (49 [62%] symptomatic, 4 [5%] asymptomatic). Eight patients (10%) developed severe COVID-19, and one died of COVID-19 pneumonia (case-fatality rate: 1.9%). The probability of SARS-CoV-2 infection was similar in children and adults (55% vs. 72%, p = .14), with children being less likely to develop the symptomatic disease (46% vs. 68%, p = .06). Handwashing ≥ 5 times/day was associated with reduced infection risk (52.8% vs. 76.9%, p = .04). SARS-CoV-2 has a high frequency of transmission among household contacts. Nonhospitalized individuals with SARS-CoV-2 infection should be quarantined in patient care facilities rather than at home to minimize spread, if possible, and frequent handwashing should be practiced to prevent transmission.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Contact Tracing/statistics & numerical data , SARS-CoV-2/pathogenicity , Adolescent , Adult , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/prevention & control , Child , Child, Preschool , Cohort Studies , Family Characteristics , Female , Hand Disinfection , Humans , Incidence , Infant , Male , Middle Aged , Quarantine , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Young Adult
20.
Pediatr Investig ; 4(4): 230-235, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-996289

ABSTRACT

IMPORTANCE: Within the coronavirus disease 2019 (COVID-19) global pandemic, more attention is warranted for whether this new infectious disease has unique manifestations in children. OBJECTIVE: To retrospectively determine the epidemiological and clinical characteristics of 35 children with COVID-19 in Beijing, China. METHODS: We collected data for 35 children diagnosed with COVID-19 who were admitted to Beijing Ditan Hospital from January 2020 to June 2020, and analyzed their epidemiological characteristics, clinical manifestations, laboratory examinations, chest imaging findings, treatments, and outcomes. RESULTS: The children comprised 18 boys (51.4%) and 17 girls (48.6%) aged 6 months to 15 years. All patients had clear epidemiological history, with family clusters accounting for 28 cases (80.0%) and clear tracing of exposure to high epidemic areas in the remaining 7 cases (20.0%). Four (11.4%) patients were classified as asymptomatic, 17 (48.6%) as acute upper respiratory infection, and 14 (40.0%) as mild pneumonia, with no severe or critical cases. Clinical manifestations were mild, including fever in 18 (51.4%), cough in 14 (40.0%), and nausea and diarrhea in 7 (20.0%) patients. White blood cell count was mostly normal (26 cases, 74.3%) or decreased (7 cases, 20.0%); lymphocyte percentage was increased in 24 (68.7%); neutrophil percentage was decreased in 25 (71.4%); alanine aminotransferase was increased in 3 (8.6%); and serum potassium was decreased in 4 (11.4%). Time to negative viral nucleic acid testing was 2-42 days (mean: 14.0 ± 9.4 days). Chest imaging examination revealed that 20 patients (57.1%) had different forms of lung inflammation. Treatment was mainly isolation and nutritional support. Eleven patients were treated with interferon atomization inhalation. No patients required oxygen therapy. All 35 children were cured and discharged. Length of hospital stay was 9-54 days (mean: 25.4 ± 13.8 days). During regular follow-up after discharge, 5 children showed positivity again in the viral nucleic acid test and were re-hospitalized for observation and treatment. The mean length of re-hospitalization stay was 10.8 days. INTERPRETATION: Children with COVID-19 mainly become infected within their family, and children of all ages are generally susceptible. The disease in children is mostly mild and the prognosis is good. Nucleic acid tests in some patients become positive again after discharge, suggesting that it is of great significance to carry out centralized isolation medical observations and active nucleic acid tests in close contacts for early detection of patients and routine epidemic prevention and control.

SELECTION OF CITATIONS
SEARCH DETAIL