Antibody titers among healthcare workers for coronavirus disease 2019 at 6 months after BNT162b2 vaccination.

BACKGROUND: Antibody levels decrease substantially at 6 months after the BNT162b2 vaccine. The factors influencing titer of antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among healthcare workers for coronavirus disease 2019 (COVID-19) is unclear. METHODS: We conducted a 6-month longitudinal prospective study in Japanese healthcare workers in a tertiary care hospital for COVID-19. Participants in the study were tested for the presence of anti-spike protein (SP) IgG antibodies before and at 1 and 6 months after the last vaccination dose. RESULTS: Among 1076 healthcare workers, 794 received the vaccine, and 469 entered the study. Five were infected with SARS-CoV-2 (none among COVID-19 section workers) by the end of the study and 451 participants were finally analyzed (mean age, 42.5 years; 27.3 % male; 18.8 % COVID-19 section workers). Median SP IgG index values were 0.0, 44.4, and 5.5 before and at 1 and 6 months after the last dose, respectively. Regression analysis revealed a negative correlation of SP IgG antibody levels with age (P < 0.0001), and higher levels in COVID-19 section workers (P = 0.0185) and in females (P = 0.0201). CONCLUSION: In healthcare workers at a COVID-19 hospital, IgG antibody titer was substantially lower at 6 months after receipt of the last dose of the BNT162b2 vaccine compared with that 1 month after the last dose, but was better preserved among younger participants, COVID-19 section workers and females.

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. METHODS: COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. RESULTS: A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. CONCLUSIONS: The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. TRIAL REGISTRATION: Clinicaltrials.jp number: JapicCTI-205238.

Clinical course and findings of 14 patients with COVID-19 compared with 5 patients with conventional human coronavirus pneumonia.

OBJECTIVE: To clarify what future problems must be resolved and how clinical findings of SARS-CoV-2 infection differ from those of cHCoV infection. METHODS: Patients and Methods Clinical characteristics of 14 patients with laboratory-confirmed Coronavirus disease 2019 (COVID-19) and 5 patients with cHCoV pneumonia admitted to our institution and treated up to March 8, 2020, were retrospectively analyzed. RESULTS: On admission, 10 patients had pneumonia, 5 of whom had pulmonary shadows detectable only via computed tomography (CT). During hospitalization, another patient with no pulmonary shadows on admission developed pneumonia. In total, 11 (78.6%) of the 14 patients developed pneumonia, indicating its high prevalence in COVID-19. During hospitalization, the patients' symptoms spontaneously relapsed and resolved, and gastrointestinal symptoms were frequently found. C-reactive protein values showed correlation with the patients' clinical courses. Ritonavir/lopinavir were administered to 5 patients whose respiratory conditions worsened during admission, all of whom improved. However, the pneumonia in the 6 other patients improved without antivirals. None of the 14 patients died, whereas 5 other patients with cHCoV pneumonia were in respiratory failure on admission, and one patient (20%) died. CONCLUSION: Both SARS-CoV-2 and cHCoV can cause severe pneumonia. Problems for future resolution include whether antiviral agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality.

[Antibody Response as Assessed by A Rapid Immunochromatographic Assay in Patients with COVID-19 Pneumonia Caused by the Novel Coronavirus, SARS-CoV-2]

An immunochromatographic assay that has been developed for the detection of antibodies in blood-derived specimens is raising expectations for the diagnosis of COVID-19, the disease caused by the novel corona virus SARS-CoV-2. Herein, we studied the interval from symptom onset to the first positive results of the immunochromatographic assay for IgM and IgG antibodies in 52 patients with a definitive diagnosis of COVID-19 (disease confirmed by the PCR test). Furthermore, we also examined the test results in 35 patients with acute fever and pneumonia who were negative by the PCR test. All patients with a definitive diagnosis of COVID-19 were confirmed to be antibody-positive. The mean time from symptom onset to the first positive result for IgM antibody was 11.9 days (minimum: 5, median: 11), and that to the first positive result for IgG antibody was 11.2 days (minimum: 5, median: 11). No significant difference was observed between the tests for IgM and IgG antibodies in terms of the percentage of positive patients or the interval from first onset to the first positive test result. There were no patients in whom the test for IgM became positive before the test for IgG. In 45 patients (87%), both IgM and IgG became positive at the same time, and in the remaining 7 patients (13%), the test for IgG became positive before that for IgM. Of 35 patients with acute fever and pneumonia who tested negative by the PCR test for SARS-CoV-2, not COVID-19, 6 (17.1%) and 1 (2.8%) showed positive results for anti-IgG antibody and anti-IgM antibody, respectively. Our study results were quite limited, and we do not intend to conduct a performance evaluation of the reagents contained in the detection kits. Assessment of antibody detection reagents for the immunochromatographic assay, which can be used as a complementary test to PCR, is expected in the future;however, the findings should be reviewed carefully.

[Predictors of Severe COVID-19 Pneumonia]

In patients with COVID-19, age over 50 years is also considered as an indication for antiviral drug therapy, in addition to hypoxemia. At this time, it still remains unclear as to which clinical markers can be considered as being predictive of severe COVID-19 pneumonia with hypoxemia. We categorized 49 patients with COVID-19 pneumonia into the following 4 groups by the clinical manifestations: stage A: no symptoms, and no viral pneumonia on chest computed tomography (CT);stage B: symptom (s) present, but no viral pneumonia on CT;stage C: viral pneumonia on CT, but no hypoxemia;stage D: viral pneumonia on CT, with hypoxemia. The clinical background characteristics that were correlated with the disease severity were the patient age, presence/absence of complications, smoking history, and presence/absence of fever and diarrhea, but multivariate analysis identified only smoking history as being significantly predictive of stage D disease. The lymphocyte count, serum CRP level, serum ferritin level and incidence of consolidation on CT were significantly different between patients with stage C and stage D disease. Therefore, we propose five predictors of severe COVID-19 pneumonia, namely, smoking history, lymphocyte count 1,200 μL, serum ferritin 400 ng/mL, serum CRP 2.5 mg/dL, and presence of consolidation on CT. The interval (in days) from the onset of symptom (s) to the first negative result of PCR for SARS-CoV2 was well correlated with the number of these risk factors in each patient (p�E�E.0001�E�E