ABSTRACT
We identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and MO3. MO1 shows high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, and BA.2.75 and BA.5. Our findings confirm that the wildtype-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants (including BA.5 and BA.2.75). The monoclonal antibodies obtained herein could serve as novel prophylaxis and therapeutics against not only current SARS-CoV-2 viruses but also future variants that may arise.
ABSTRACT
The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n=23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Surprisingly and interestingly, after the second vaccination, the subjects neutralizing antibody titers including that against Omicron all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the subjects disease severity. Our findings thus demonstrate that at least two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.
ABSTRACT
In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but is not firmly established. We investigated the neutralizing potency of 81 COVID-19 patients sera from 4 waves of pandemic against SARS-CoV-2 variants using their authentic viruses. Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351.
ABSTRACT
Background@#Neutralizing antibody cocktail therapy, REGN-COV2, is promising in preventing a severe form of coronavirus disease 2019 (COVID-19), but its effectiveness in Japan has not been fully investigated. @*Materials and Methods@#To evaluate the effectiveness of REGN-COV2, clinical data of 20 patients with COVID-19 who received REGN-COV2 was compared with the control by matching age and sex. The primary outcome was the time from the onset to defervescence, the duration of hospitalization, and oxygen requirement. A sensitivity analysis using Bayesian analysis was also conducted. @*Results@#The time to defervescence was significantly shorter in the treatment group (5.25 vs. 7.95 days, P = 0.02), and so was the duration of hospitalization (7.115 vs. 11.45, P = 0.0009). However, the oxygen therapy requirement did not differ between the two groups (15% vs. 35%, P = 0.27). For Bayesian analysis, the median posterior probability of the time to defervescence since the symptom onset on the REGN-COV2 group was 5.28 days [95% credible interval (CrI): 4.28 - 6.31 days], compared with the control of 7.99 days (95% CrI: 6.81 - 9.24 days). The posterior probability of the duration of the hospitalization on the REGN-COV2 group was 7.17 days (95% CrI: 5.99 - 8.24 days), compared with the control of 11.54 days (95% CrI: 10.28 - 13.14 days). The posterior probability of the oxygen requirement on the REGN-COV2 group was 18% (95% CrI: 3 - 33%), compared with the control of 36% (95% CrI: 16 - 54%). @*Conclusion@#REGN-COV2 may be effective in early defervescence and shorter hospitalization. Its effectiveness for preventing a severe form of infection needs to be evaluated by further studies.
ABSTRACT
ObjectivesAli-M3, an artificial intelligence, analyses chest computed tomography (CT) and detects the likelihood of coronavirus disease (COVID-19) in the range of 0 to 1. It demonstrates excellent performance for the detection of COVID-19 patients with a sensitivity and specificity of 98.5 and 99.2%, respectively. However, Ali-M3 has not been externally validated. Our purpose is to evaluate the external validity of Ali-M3 using Japanese sequential sampling data. MethodsIn this retrospective cohort study, COVID-19 infection probabilities were calculated using Ali-M3 in 617 symptomatic patients who underwent reverse transcription-polymerase chain reaction (RT-PCR) tests and chest CT for COVID-19 diagnosis at 11 Japanese tertiary care facilities, between January 1 and April 15, 2020. ResultsOf 617 patients, 289 patients (46.8%) were RT-PCR-positive. The area under the curve (AUC) of Ali-M3 for predicting a COVID-19 diagnosis was 0.797 (95% confidence intervals [CI]: 0.762-0.833) and goodness-of-fit was P = 0.156. With a cut-off of probability of COVID-19 by Ali-M3 diagnosis set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively, while a cut-off of 0.2 yielded a sensitivity and specificity of 89.2% and 43.2%, respectively. Among 223 patients who required oxygen support, the AUC was 0.825 and sensitivity at a cut-off of 0.5 and 0.2 were 88.7% and 97.9%, respectively. Although the sensitivity was lower when the days from symptom onset were few, sensitivity increased for both cut-off values after 5 days. ConclusionsAli-M3 was evaluated by external validation and shown to be useful to exclude a diagnosis of COVID-19. Key PointsO_LIThe area under the curve (AUC) of Ali-M3, which is an AI system for diagnosis of COVID-19 based on chest CT images, was 0.797 and goodness-of-fit was P = 0.156. C_LIO_LIWith a cut-off of probability of COVID-19 by Ali-M3 diagnosis set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively, while a cut-off of 0.2 yielded 89.2% and 43.2%. C_LIO_LIAlthough low sensitivity was observed in less number of days from symptoms onset, after 5 days high increasing sensitivity was observed. In patients requiring oxygen support, the AUC was higher that is 0.825. C_LI
ABSTRACT
BackgroundCOVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease, and older individuals are known to be affected more severely. Neutralizing antibody for viruses is critical for their elimination, and increased cytokine/chemokine levels are thought to be related to COVID-19 severity. However, the trend of the neutralizing antibody production and cytokine/chemokine levels during the clinical course of COVID-19 patients with differing levels of severity has not been established. MethodsWe serially collected 45 blood samples from 12 patients with different levels of COVID-19 severity, and investigated the trend of neutralizing antibody production using authentic SARS-CoV-2 and cytokine/chemokine release in the patients clinical courses. ResultsAll 12 individuals infected with SARS-CoV-2 had the neutralizing antibody against it, and the antibodies were induced at approx. 4-10 days after the patients onsets. The antibodies in the critical and severe cases showed high neutralizing activity in all clinical courses. Most cytokine/chemokine levels were clearly high in the critical patients compared to those with milder symptoms. ConclusionNeutralizing antibodies against SARS-CoV-2 were induced at a high level in the severe COVID-19 patients, indicating that abundant virus replication occurred. Cytokines/chemokines were expressed more in the critical patients, indicating that high productions of cytokines/chemokines have roles in the disease severity. These results may indicate that plasma or neutralizing antibody therapy could be a first-line treatment for older patients to eliminate the virus, and corticosteroid therapy could be effective to suppress the cytokine storm after the viral genomes disappearance.
