The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force.

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

Frequency and Significance of Coinfection in Patients with COVID-19 at Hospital Admission.

Objective Viral pneumonia is not rare in community-acquired pneumonia (CAP). Mixed or secondary pneumonia (coinfection) can be seen in viral pneumonia; however, its frequency in coronavirus disease 2019 (COVID-19) has only been investigated in a few studies of short duration, and its significance has not been fully elucidated. We investigated the frequency and significance of co-infection in patients with COVID-19 over a 1-year study period. Methods Coinfection was investigated via multiplex polymerase chain reaction (PCR), culture of respiratory samples, rapid diagnostic tests, and paired sera. We used logistic regression analysis to analyze the effect of coinfection on severity at admission and Cox proportional-hazards model analysis to analyze the effect of coinfection on need for high-flow nasal cannula, invasive mandatory ventilation use, and death, respectively. Patients We retrospectively investigated 298 patients who suffered CAP due to severe acute respiratory syndrome coronavirus-2 infection diagnosed by PCR and were admitted to our institution from February 2020 to January 2021. Results Primary viral pneumonia, and mixed viral and bacterial pneumonia, accounted for 90.3% and 9.7%, respectively, of COVID-19-associated CAP, with viral coinfection found in 30.5% of patients with primary viral pneumonia. Influenza virus was the most common (9.4%). Multivariable analysis showed coinfection not to be an independent factor of severity on admission, need for high-flow nasal cannula or invasive mandatory ventilation, and mortality. Conclusion Viral coinfection was common in COVID-19-associated CAP. Severity on admission, need for high-flow oxygen therapy or invasive mandatory ventilation, and mortality were not affected by coinfection.

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