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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22271262

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.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-21258682

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.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-20168682

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.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-20107490

ABSTRACT

The analysis of systematically collected data for COVID-19 infectivity and death rates has revealed in many countries around the world a typical oscillatory pattern with a 7-days (circaseptan) period. Additionally, in some countries the 3.5-days (hemicircaseptan) and 14-days periodicities have been also observed. Interestingly, the 7-days infectivity and death rates oscillations are almost in phase, showing local maxima on Thursdays/Fridays and local minima on Sundays/Mondays. These observations are in stark contrast with a known pattern, correlating the death rate with the reduced medical staff in hospitals on the weekends. One possible hypothesis addressing these observations is that they reflect a gradually increasing stress with the progressing week, which can trigger the maximal death rates observed on Thursdays/Fridays. Moreover, assuming the weekends provide the likely time for new infections, the maximum number of new cases might fall again on Thursdays/Fridays. These observations deserve further study to provide better understanding of the COVID-19 dynamics.

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