Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

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Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19

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COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

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Characteristics of immune cells and cytokines in patients with coronavirus disease 2019 in Guangzhou,China

To discover immune factors that can predict the progression of COVID-19, we evaluated circulating immune cells and plasma cytokines in COVID-19 patients. We found that T cells, including CD4⁺ T cells and CD8⁺ T cells, were significantly decreased in severe COVID-19 symptoms but not in mild symptoms, in comparison with healthy people. T cells remained at a low level after recovery from severe COVID-19. CD4⁺CD25⁺CD127^low Treg-enriched cells were significantly increased in either mild or severe COVID-19 patients, regardless of recovery or not. Moreover, in either mild or severe COVID-19 patients, Treg-enriched cells up-regulated CD25 and down-regulated CD127. After recovery, CD25 was partially down-regulated but still higher than the normal level, while CD127 returned to the normal level in mild patients but not severe patients. B cells were decreased in mild patients and further decreased in severe patients, and remained low after recovery. NK cells were decreased only in severe COVID-19, with a tendency to return to the normal level after recovery. Plasma IL-6 and IL-10 were both elevated in severe patients but not in mild patients. After recovery, IL-6 remained higher than its normal level, while IL-10 returned to the normal level. Binary logistic regression analysis indicated that CD4⁺ T cells, B cells, IL-6, and IL-10 were significantly associated with COVID-19 severity. Therefore, these parameters are indicators of COVID-19 severity. Dynamic monitoring of these parameters would benefit therapy planning and prognosis evaluation.     

Detection of parvovirus B19 in the lower respiratory tract

BackgroundHuman parvovirus B19 infection generally displays a self-limiting course followed by viral clearance; although, in some cases, persistent infection may occur. Few cases of severe pulmonary disease following primary infection in both immunocompetent and immunocompromised patients were reported.ObjectivesTo investigate the prevalence and clinical impact of parvovirus B19 in the lower respiratory tract.Study designThe prevalence of parvovirus B19-DNA was evaluated by Real-Time PCR in 264 bronchoalveolar lavages (BAL) from 189 adult patients over a full-year period and related to demographic characteristics, underlying pathologies, immune status, admission to intensive care unit, mortality within 28 days, and discharge diagnosis.ResultsParvovirus B19-DNA was detected in 7/189 (3.7%) patients, without significant association to demographic characteristics, immune status, transplant versus non-transplant status, admission to intensive care unit, presence of haematological conditions. In two lung transplant recipients surveillance specimens were positive to B19. Four of the remaining five patients presented respiratory insufficiency. A significant association to mortality was found, as 3/7 (42.9%) positive patients died within 28 days. No patient presented serological evidence of recent or acute infection and viremia.ConclusionsParvovirus B19 may be detected at low frequency in BAL specimens from patients with different pathological backgrounds. This finding could be due to chronic infection with virus persistence in the lower respiratory tract, also in the absence of symptoms unequivocally attributable to B19. The high rate of mortality warrants the need for further studies to evaluate the opportunity to consider parvovirus B19 in the diagnostic work-up of lower respiratory tract infections.     

Approaching COVID-19 with epidemiological genomic surveillance and the sustainability of biodiversity informatics in Africa

COVID-19 is an acute respiratory illness caused by Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). The first case was reported in Africa on February 14, 2020 and has surged to 11 million as of July 2022, with 43% and 30% of cases in Southern and Northern Africa. Current epidemiological data demonstrate heterogeneity in transmission and patient outcomes in Africa. However, the burden of infectious diseases such as malaria creates a significant burden on public health resources that are dedicated to COVID-19 surveillance, testing, and vaccination access. Several control measures, such as the SHEF2 model, encompassed Africa's most effective preventive measure. With the help of international collaborations and partnerships, Africa's pandemic preparedness employs effective risk-management strategies to monitor patients at home and build the financial capacity and human resources needed to combat COVID-19 transmission. However, the lack of safe sanitation and inaccessible drinking water, coupled with the financial consequences of lockdowns, makes it challenging to prevent the transmission and contraction of COVID-19. The overwhelming burden on contact tracers due to an already strained healthcare system will hurt epidemiological tracing and swift counter-measures. With the rise in variants, African countries must adopt genomic surveillance and prioritize funding for biodiversity informatics.     

Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

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No correlation between Ct values and severity of disease or mortality in patients with COVID 19 disease

There are several reports of Ct values of RT PCR assays for COVID 19 being associated with disease severity and infectivity. We studied the correlation between Ct values and disease severity and mortality at our hospital . All patients with RT PCR diagnosed COVID 19 illness admitted at the study site and for whom Ct values were available were included in the study. The patients with mild disease had significantly lower Ct values than patients with severe disease but had also been tested significantly earlier in the illness than those with severe disease. The patients who died had significantly lower Ct values than patients who survived but here again they had significantly shorter duration of symptoms before testing. We therefore recommend that the time of testing since onset of symptoms should be controlled for while correlating Ct values with disease severity.     

An unusual COVID-19 case with over four months of viral shedding in the presence of low neutralizing antibodies: a case report

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis, causing social and economic disasters in many countries. In China, two-consecutive negative results of nucleic acid tests for SARS-CoV-2 from the respiratory samples are required to end the quarantine of COVID-19 patients. However, clinicians face a dilemma in case of patients with long-term viral shedding. This report described an unusual COVID-19 case who had persistent viral RNA positivity for more than 4 months after initial illness in the presence of low neutralizing antibodies, but without prolonged clinical symptoms. Multiple anti-viral drug treatments had no impact and there was no evidence of re-infection. When the patient was self-quarantined at home, no infection occurred to the three family members living with her for 15 to 19 days. Sputum viral culture in BSL-3 laboratory on the 102^nd day after symptom onset was negative. From the 129^th day on, 8 continuous nucleic acid tests of sputum samples showed negative results. The patient was discharged on 137^th days since symptom onset. In conclusion, viral RNA shedding in the sputum of the COVID-19 patient may last over 4 months. As no evidence shows the existence of infectious virus, two-consecutive negative nucleic acid tests may not be the prerequisite for ending quarantine of COVID-19 patients with prolonged viral shedding.     

Impact of the COVID-19 pandemic on pathological autopsy practices in Japan

During the coronavirus disease 2019 (COVID-19) pandemic, autopsies have provided valuable insights into the pathogenesis of COVID-19. The precise effect of this pandemic on autopsy procedures in Japan, especially in instances unrelated to COVID-19, has not yet been established. Therefore, we conducted a questionnaire survey from December 2020 to January 2021 regarding the status of pathological autopsy practices in Japan during the first year of the COVID-19 pandemic. The questionnaire was sent to 678 medical facilities with pathologists, of which 227 responded. In cases where a confirmed diagnosis of COVID-19 was not made at the time of autopsy, many facilities counted them as suspected COVID-19 cases if pneumonia was suspected clinically. At around half of the sites, autopsies were prohibited for suspected COVID-19 cases. In addition, the number of autopsies of non-COVID-19 cases during the pandemic period was also investigated, and a significant decrease was observed compared with the incidence in the pre-pandemic period. The COVID-19 pandemic has affected not only the autopsies of COVID-19 cases but also the entire practice of pathological autopsies. It is necessary to establish a system that supports the implementation of pathological autopsy practices during the pandemic of an emerging infectious disease.     

Characteristics and roles of severe acute respiratory syndrome coronavirus 2-specific antibodies in patients with different severities of coronavirus 19

The diagnosis of coronavirus 19 (COVID-19) relies mainly upon viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody detection is convenient, safe and highly sensitive. Immunoglobulin (Ig)M and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. COVID-19 patients, divided into a severe and critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results and other data were recorded for all patients. Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are more effective for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe and critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Detection of SARS-CoV-2-specific combined IgA–IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.