A meta-analysis result: Uneven influences of season, geo-spatial scale and latitude on relationship between meteorological factors and the COVID-19 transmission.

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies; (2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.

The anti-C5a antibody vilobelimab efficiently inhibits C5a in patients with severe COVID-19.

Recently, we reported the phase II portion of the adaptive phase II/III PANAMO trial exploring potential benefit and safety of selectively blocking C5a with the monoclonal antibody vilobelimab (IFX-1) in patients with severe coronavirus disease 2019 (COVID-19). The potent anaphylatoxin C5a attracts neutrophils and monocytes to the infection site, causes tissue damage by oxidative radical formation and enzyme releases, and leads to activation of the coagulation system. Results demonstrated that C5a inhibition with vilobelimab was safe and secondary outcomes appeared in favor of vilobelimab. We now report the pharmacokinetic/pharmacodynamic (PK/PD) analysis of the phase II study. Between March 31 and April 24, 2020, 30 patients with severe COVID-19 pneumonia confirmed by real-time polymerase chain reaction were randomly assigned 1:1 to receive vilobelimab plus best supportive care or best supportive care only. Samples for measurement of vilobelimab, C3a and C5a blood concentrations were taken. Vilobelimab predose (trough) drug concentrations in plasma ranged from 84,846 to 248,592 ng/ml (571 to 1674 nM) with a geometric mean of 151,702 ng/ml (1022 nM) on day 2 and from 80,060 to 200,746 ng/ml (539 to 1352 nM) with a geometric mean of 139,503 ng/ml (939 nM) on day 8. After the first vilobelimab infusion, C5a concentrations were suppressed in the vilobelimab group (median 39.70 ng/ml 4.8 nM, IQR 33.20-45.55) as compared to the control group (median 158.53 ng/ml 19.1 nM, IQR 60.03-200.89, p = 0.0006). The suppression was maintained on day 8 (p = 0.001). The current PK/PD analysis shows that vilobelimab efficiently inhibits C5a in patients with severe COVID-19.

Impacts of socio-economic determinants, spatial distance and climate factors on the confirmed cases and deaths of COVID-19 in China.

This study is to assess the influences of climate, socio-economic determinants, and spatial distance on the confirmed cases and deaths in the raise phase of COVID-19 in China. The positive confirmed cases and deaths of COVID-19 over the population size of 100,000 over every 5 consecutive days (the CCOPSPTT and DOPSPTT for short, respectively) covered from 25th January to 29th February, 2020 in five city types (i.e., small-, medium-, large-, very large- and super large-sized cities), along with the data of climate, socio-economic determinants, spatial distance of the target city to Wuhan city (DW, for short), and spatial distance between the target city and their local province capital city (DLPC, for short) were collected from the official websites of China. Then the above-mentioned influencing factors on CCOPSPTT and DOPSPTT were analyzed separately in Hubei and other provinces. The results showed that CCOPSPTT and DOPSPTT were significantly different among five city types outside Hubei province (p < 0.05), but not obviously different in Hubei province (p > 0.05). The CCOPSPTT had significant correlation with socio-economic determinants (GDP and population), DW, climate and time after the outbreak of COVID-19 outside Hubei province (p < 0.05), while was only significantly related with GDP in Hubei province (p < 0.05). The DOPSPTT showed significant correlation with socio-economic determinants, DW, time and CCOPSPTT outside Hubei province (p < 0.05), while was significantly correlated with GDP and CCOPSPTT in Hubei province (p < 0.05). Compared with other factors, socio-economic determinants have the largest relative contribution to variance of CCOPSPTT in all studied cities (> 78%). The difference of DOPSPTT among cities was mainly affected by CCOPSPTT. Our results showed that influences of city types on the confirmed cases and death differed between Hubei and other provinces. Socio-economic determinants, especially GDP, have higher impact on the change of COVID-19 transmission compared with other factors.

The Positive Role of Tai Chi in Responding to the COVID-19 Pandemic.

The ongoing coronavirus 2019 (COVID-19) pandemic has posed a significant threat to both people's physical and mental health. Physical inactivity, sedentary behavior, and negative emotions among the general population have been significantly increased because of COVID-19 home confinement. These are major risk factors associated with higher incidences of morbidity and mortality. Therefore, effective exercise management should be proposed as a prevention strategy to improve both physical and mental health while diminishing the effects of COVID-19. Tai Chi as a low-to-moderate aerobic exercise combines physical and mental training and plays a positive impact on human health. Here we aim to outline the effects of Tai Chi on the immune system, inflammatory responses, pulmonary function, and emotional control. The benefits of Tai Chi practice for individuals coping with COVID-19 are stated here which include immune system promotion, inflammation response reduction, rehabilitation in respiratory diseases, and emotional improvement. This statement has been supported by available clinical, physiological, and biological research. As a result, we hope to introduce Tai Chi as an effective exercise intervention for people coping with COVID-19 and as a beneficial exercise for maintaining an active lifestyle during a pandemic.

Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial.

BACKGROUND: Severe COVID-19 is characterised by inflammation and coagulation in the presence of complement system activation. We aimed to explore the potential benefit and safety of selectively blocking the anaphylatoxin and complement protein C5a with the monoclonal antibody IFX-1 (vilobelimab), in patients with severe COVID-19. METHODS: We did an exploratory, open-label, randomised phase 2 trial (part of the adaptive phase 2/3 PANAMO trial) of intravenous IFX-1 in adults with severe COVID-19 at three academic hospitals in the Netherlands. Eligibility criteria were age 18 years or older; severe pneumonia with pulmonary infiltrates consistent with pneumonia, a clinical history of severe shortness of breath within the past 14 days, or a need for non-invasive or invasive ventilation; severe disease defined as a ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) between 100 mm Hg and 250 mm Hg in the supine position; and severe acute respiratory syndrome coronavirus 2 infection confirmed by RT-PCR. Patients were randomly assigned 1:1 to receive IFX-1 (up to seven doses of 800 mg intravenously) plus best supportive care (IFX-1 group) or best supportive care only (control group). The primary outcome was the percentage change in PaO2/FiO2 in the supine position between baseline and day 5. Mortality at 28 days and treatment-emergent and serious adverse events were key secondary outcomes. The primary analysis was done in the intention-to-treat population and safety analyses were done in all patients according to treatment received. This trial is registered at ClinicalTrials.gov (NCT04333420). FINDINGS: Between March 31 and April 24, 2020, 30 patients were enrolled and randomly assigned to the IFX-1 group (n=15) or the control group (n=15). During the study it became clear that several patients could not be assessed regularly in the supine position because of severe hypoxaemia. It was therefore decided to focus on all PaO2/FiO2 assessments (irrespective of position). At day 5 after randomisation, the mean PaO2/FiO2 (irrespective of position) was 158 mm Hg (SD 63; range 84-265) in the IFX-1 group and 189 mm Hg (89; 71-329) in the control group. Analyses of the least squares mean relative change in PaO2/FiO2 at day 5 showed no differences between treatment groups (17% change in the IFX-1 group vs 41% in the control group; difference -24% [95% CI -58 to 9], p=0·15. Kaplan-Meier estimates of mortality by 28 days were 13% (95% CI 0-31) for the IFX-1 group and 27% (4-49) for the control group (adjusted hazard ratio for death 0·65 [95% CI 0·10-4·14]). The frequency of serious adverse events were similar between groups (nine [60%] in the IFX-1 group vs seven [47%] in the control group) and no deaths were considered related to treatment assignment. However, a smaller proportion of patients had pulmonary embolisms classed as serious in the IFX-1 group (two [13%]) than in the control group (six [40%]). Infections classed as serious were reported in three (20%) patients in the IFX-1 group versus five (33%) patients in the control group. INTERPRETATION: In this small exploratory phase 2 part of the PANAMO trial, C5a inhibition with IFX-1 appears to be safe in patients with severe COVID-19. The secondary outcome results in favour of IFX-1 are preliminary because the study was not powered on these endpoints, but they support the investigation of C5a inhibition with IFX-1 in a phase 3 trial using 28-day mortality as the primary endpoint. FUNDING: InflaRx.

Anti-C5a Antibody (IFX-1) Treatment of Severe COVID-19: An Exploratory Phase 2 Randomized Controlled Trial (preprint)

Background: Severe coronavirus disease 2019 (Covid-19) is characterized by inflammation and coagulation in the presence of complement activation. Methods: We conducted an explorative phase 2 randomized, open label first part of an adaptive phase 2/3 trial of intravenous IFX-1, a monoclonal antibody selectively blocking the anaphylatoxin C5a, in adults with severe Covid-19. Patients were randomized between IFX-1 plus best supportive care (BSC) or BSC only. Results: 30 patients underwent randomization: 15 assigned to IFX-1 and 15 to BSC. PaO2/FiO2 ratio improvement on day 5, chosen as primary outcome parameter, did not show significant differences between groups. However, IFX-1 treatment was associated with consistent trends of improvement as evidenced by lower mortality rate, reduction in renal impairment, normalization of lymphocyte counts, and lowering of plasma lactate dehydrogenase concentrations. Kaplan-Meier estimates of mortality by 28 days were 13% for IFX-1 and 27% for BSC (HR for death, 0.56; 95%CI 0.09-3.74). Serious adverse events rates were comparable between groups but the rate of pulmonary embolisms was three-fold lower in the IFX-1 group (13%) compared to BSC group (40%). IFX-1 treatment was associated with significant increase of D-dimer levels suggesting a potential pro-fibrinolytic activity of anti-C5a treatment. Conclusion: In this exploratory part of the study, C5a inhibition with IFX-1 was shown to be safe in severe Covid-19. PaO2/FiO2 ratio at day five was comparable between groups, but consistent signals of benefit including a lower 28-day all-cause mortality rate, lower rate in impaired kidney function and a lower rate of pulmonary embolism warrant investigating C5a-inhibition with IFX-1 within a phase 3 trial.Trial Registration: This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov (NCT04333420). Funding Statement: The trial is funded by InflaRx GmbH.Declaration of Interests: NR and RG are founders, active officers and executive directors of InflaRx (InflaRx GmbH, InflaRx Pharmaceuticals Inc. and InflaRx N.V.) and hold shares and stock options in InflaRx. KP is Global Head of Clinical Development of InflaRx and holds stock options in InflaRx. SR is employee at Metronomia, a contracted statistical service provider for InflaRx. MW is supported by grants from the German Research Foundation, SFB-TR84 C6 and C9 and by the German Ministry of Education and Research in the framework of the CAPSyS (01ZX1304B) and the PROVID project (FKZ 01KI20160A). DvdB reports receiving departmental honoraria for serving on a scientific advisory board for InflaRx in 2017, paid to Amsterdam UMC. All other authors have no Conflict of Interest. Ethics Approval Statement: The study protocol was approved by the institutional review board of the Academic Medical Center, part of Amsterdam UMC, Amsterdam, the Netherlands (IRB: 2020_067#B2020179). If direct informed consent of patients was not feasible, patients could be included with a deferred consent procedure. All patients or their legally authorized representatives gave written informed consent for the study.

Benefits of Exercise on Influenza or Pneumonia in Older Adults: A Systematic Review.

A coronavirus pandemic has recently become one of the greatest threats the world is facing. Older adults are under a high risk of infection because of weaker immune systems. Therefore, the purpose of this review is to summarize the recent scientific evidence that outlines the effects of exercise on influenza or pneumonia in older adults. An electronic literature search was conducted using the WEB OF SCIENCE, SCIENCEDIRECT and GOOGLE SCHOLAR databases using the following keywords, "Exercise," "Older adult," "Influenza," and "Pneumonia." Any randomized control trials, cross-sectional and observational studies that related to this topic were all included. Twenty studies met the eligibility criteria for this review. Thirteen randomized control trials investigated the effects of exercise on the immune responses to influenza or pneumonia vaccination: seven trials employed moderate aerobic exercise, three employed resistance exercise, and the remaining three used Asian martial arts or special home-based exercises. Five cross-sectional and two observational studies examined the associations between exercise/physical condition and influenza/pneumonia. Most of the current studies suggested that prolonged moderate aerobic exercise may help to reduce the risk of influenza-related infection and improve the immune responses to influenza or pneumonia vaccination in older adults. In addition, training in traditional Asian martial arts was also found to be beneficial. Future research should focus on the different effects of moderate and vigorous exercise on influenza-related diseases.