Longitudinal Serum Proteome Characterization of COVID-19 Patients With Different Severities Revealed Potential Therapeutic Strategies.

The COVID-19 pandemic caused by SARS-CoV-2 is exerting huge pressure on global healthcare. Understanding of the molecular pathophysiological alterations in COVID-19 patients with different severities during disease is important for effective treatment. In this study, we performed proteomic profiling of 181 serum samples collected at multiple time points from 79 COVID-19 patients with different severity levels (asymptomatic, mild, moderate, and severe/critical) and 27 serum samples from non-COVID-19 control individuals. Dysregulation of immune response and metabolic reprogramming was found in severe/critical COVID-19 patients compared with non-severe/critical patients, whereas asymptomatic patients presented an effective immune response compared with symptomatic COVID-19 patients. Interestingly, the moderate COVID-19 patients were mainly grouped into two distinct clusters using hierarchical cluster analysis, which demonstrates the molecular pathophysiological heterogeneity in COVID-19 patients. Analysis of protein-level alterations during disease progression revealed that proteins involved in complement activation, the coagulation cascade and cholesterol metabolism were restored at the convalescence stage, but the levels of some proteins, such as anti-angiogenesis protein PLGLB1, would not recovered. The higher serum level of PLGLB1 in COVID-19 patients than in control groups was further confirmed by parallel reaction monitoring (PRM). These findings expand our understanding of the pathogenesis and progression of COVID-19 and provide insight into the discovery of potential therapeutic targets and serum biomarkers worth further validation.

Cash, COVID-19 and aid cuts: a mixed-method impact evaluation among South Sudanese refugees registered in Kiryandongo settlement, Uganda.

OBJECTIVES: In this paper, we estimate the impact after 4-8 months of a large one-off unconditional cash transfer delivered to refugees during a time of dual shocks: the COVID-19 pandemic and cuts to monthly aid. We focus on four key outcomes: (1) health-seeking behaviour; (2) COVID-19 specific preventive health practices; (3) food security and (4) psychological well-being. METHODS: We use both quantitative and qualitative data to understand the impact of a cash transfer in this context. Quantitatively, we use a baseline survey of 1200 households (Q4 2019) and follow-up with three rounds of phone surveys in Q2 and Q3 2021, capturing at least half the sample in each round. We exploit an experimental variation in the timing of the cash transfer to assess the effect of the cash transfer through ordinary least squares regressions of intention to treat. Controlling for key baseline characteristics, we analyse the effect of the cash transfer on health access, COVID-19 health practices, food security and psychological well-being. Qualitatively, we make use of a longitudinal, small-n sample of refugee respondents, each of whom we interviewed up to 15 times between February and September 2020 to understand change over time and to go deeper into key topics. RESULTS: We do not find a statistically significant effect (6.2%, p=0.188) of receiving the cash transfer on preventative measures against COVID-19. However, households receiving the cash transfer were more food secure, with a 14.4% (p=0.011) improvement on the food security index, have better psychological well-being (24.5%, p=0.003) and are more likely to seek healthcare in the private health facilities (10.4%, p=0.057) as compared with control households. We do not find significant results on the value of food consumption. Overall, we find stronger treatment effects for households that were the first to receive the cash transfers. CONCLUSION: Taken together, we find significant support for the importance of cash transfers to refugee households mitigating against declines in food security and mental well-being in the face of shocks.

Early Use of Corticosteroid May Prolong SARS-CoV-2 Shedding in Non-Intensive Care Unit Patients with COVID-19 Pneumonia: A Multicenter, Single-Blind, Randomized Control Trial.

BACKGROUND: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. OBJECTIVE: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. METHODS: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. RESULTS: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). CONCLUSIONS: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04273321.

Impact of SARS-CoV-2 on Male Reproductive Health: A Review of the Literature on Male Reproductive Involvement in COVID-19.

Coronavirus Disease 2019 (COVID-19) has created a global pandemic. Global epidemiological results show that elderly men are susceptible to infection of COVID-19. The difference in the number of cases reported by gender increases progressively in favor of male subjects up to the age group ≥60-69 (66.6%) and ≥70-79 (66.1%). Through literature search and analysis, we also found that men are more susceptible to SARS-CoV-2 infection than women. In addition, men with COVID-19 have a higher mortality rate than women. Male represents 73% of deaths in China, 59% in South Korea, and 61.8% in the United States. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen of COVID-19, which is transmitted through respiratory droplets, direct and indirect contact. Genomic analysis has shown that SARS-CoV-2 is 79% identical to SARS-CoV, and both use angiotensin-converting enzyme 2 (ACE2) as the receptor for invading cells. In addition, Transmembrane serine protease 2 (TMPRSS2) can enhance ACE2-mediated virus entry. However, SARS-CoV-2 has a high affinity with human ACE2, and its consequences are more serious than other coronaviruses. ACE2 acts as a "gate" for viruses to invade cells and is closely related to the clinical manifestations of COVID-19. Studies have found that ACE2 and TMPRSS2 are expressed in the testis and male reproductive tract and are regulated by testosterone. Mature spermatozoon even has all the machinery required to bind SARS-CoV-2, and these considerations raise the possibility that spermatozoa could act as potential vectors of this highly infectious disease. This review summarizes the gender differences in the pathogenesis and clinical manifestations of COVID-19 and proposes the possible mechanism of orchitis caused by SARS-CoV-2 and the potential transmission route of the virus. In the context of the pandemic, these data will improve the understanding of the poor clinical outcomes in male patients with COVID-19 and the design of new strategies to prevent and treat SARS-CoV-2 infection.

Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China.

Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%.Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia.Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020.Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively.Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.