Moderate Pneumonia Research Articles

The importance of overweight in COVID-19: A retrospective analysis in a single center of Wuhan, China.

The aim of this study was to evaluate the association between overweight and severity, drug response, and clinical outcomes of novel coronavirus disease 2019 (COVID-19).In this retrospective cohort study, we reviewed medical records of 240 COVID-19 patients admitted to Union Hospital in Wuhan, China, between December 24, 2019, and March 25, 2020. Physical, clinical, laboratory, radiological characteristics, treatment, and outcome data were abstracted. Patients who were obese [body mass index (BMI) ≥28 kg/m2], underweight (BMI < 18.5 kg/m2), under 18 years old, pregnant, or still in hospital were excluded. Disease severity was classified as moderate or severe pneumonia based on the World Health Organization interim guidance. Overweight was defined as BMI ≥24 kg/m2 and <28 kg/m2. Patients were followed for discharge or death through April 10, 2020. We used logistic regression models to identify risk factors for severe disease, Cox proportional hazard models to explore associations between medications and patient outcomes (discharge or in-hospital death), and Kaplan–Meier survival curves and Cox regression models to evaluate risk factors for in-hospital death.One-half of patients (120, 50.0%) had severe pneumonia, while nearly one-half (114, 47.5%) were overweight. Among patients over 45 years old, overweight patients had significantly lower rates of fatigue, higher rates of headache, and higher median C-reactive protein levels. Patients under 45 years old had higher rates of cough and myalgia and higher proportions of increased alanine aminotransferase and lactic dehydrogenase, as well as more pulmonary lobes involved in the pneumonia revealed by chest computed tomography scans. Overweight patients were at higher risk of developing severe pneumonia. Although weight was not a risk factor for in-hospital death, overweight patients showed different responses to medications compared with normal weight patients. Intravenous interferon-α, intravenous glucocorticoids, and antifungal drugs were associated with reduced mortality in overweight patients. Intravenous immunoglobulin, oseltamivir, and ribavirin were associated with reduced mortality in normal weight patients.Overweight is a worldwide health problem. We found overweight to be related to the COVID-19 severity but not to in-hospital death. Clinicians should be aware that overweight COVID-19 patients require increased attention for different clinical features and treatment response.

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild–moderate, severe–critical, and chronic–fibrotic). In susceptible individuals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33–ST2 axis might act to expand the number of pathogenic granulocyte–macrophage colony-stimulating factor-expressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelial–mesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.

Early prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.

Modeling SARS-CoV-2 in mice

Coronavirus Among the research tools necessary to develop medical interventions to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, high on the list are informative animal models with which to study viral pathogenesis. Gu et al. developed a mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia. Adaptation of this viral strain in the mouse appeared to be dependent on a critical amino acid change, Asn501 to Tyr (N501Y), within the receptor-binding domain of the viral spike protein. The new mouse model was used to study neutralizing antibodies and a vaccine candidate against the virus. Science , this issue p. [1603][1] [1]: /lookup/doi/10.1126/science.abc4730

Neutrophil Oxidized-Modified Proteins and Neutrophil Extracellular Traps in Patients with Community-Acquired Pneumonia.

Materials and Methods 51 patients with CAP were divided into 2 groups depending on the severity of the pathological process. The first group (I) consisted of 32 patients with moderate severity of pneumonia. The second group (II) consisted of 19 patients with severe pneumonia. The third group (III), the comparison group, consisted of 14 CAP patients with chronic obstructive pulmonary disease (COPD). The control group consisted of 19 volunteers. Results Statistically significant increase in the level of carbonyl derivatives (CD) in patients of all study groups relative to the control group was revealed. In the group of patients with moderate severity and severe pneumonia, also in CAP patients with COPD, the level of CD exceeded the control group. There was no statistically significant difference in the level of advanced oxidation protein products (AOPP) and myeloperoxidase (MPO) in blood neutrophils between the studied groups. Conclusion Results indicate an oxidative imbalance in neutrophils and contribute to the worsening of the course of the disease.

Covid-19 in a patient with ANCA-associated systemic vasculitis, receiving anti-B cell therapy (rituximab)

Despite numerous publications on COVID-19, at present, conceptual thinking of the problem is only at a nascence stage. Treatment of patients with ANCA-associated systemic vasculitis (AAV) during the COVID-19 pandemic is one of the relevant issues. Management of COVID-19 in AAV patients undergoing anti-B cell therapy with rituximab (RTM) requires comprehensive reasoning. This paper presents a case report about COVID-19 in a 59-year-old female with AAV in remission, who was previously treated with RTM. COVID-19 was diagnosed one month after the last RTM administration; there were moderate bilateral pneumonia, fever, and extrapulmonary manifestations, including lesions of the gastrointestinal tract and central nervous system. Clinical outcome of COVID-19 was favorable, with no signs of respiratory failure, and CRP values did not exceed 29 mg/l. We discuss published data on RTM use during COVID-19 pandemic and the effects of B cells and their depletion on the course and outcomes of COVID-19. Our case report and available published data do not allow to consider RTM therapy as a factor associated with severe course of COVID-19 and adverse outcome. Further analysis of COVID-19 in patients with AAV and other rheumatic diseases is important.

Compassionate use of convalescent plasma for treatment of moderate and severe pneumonia in COVID-19 patients and association with IgG antibody levels in donated plasma.

BackgroundWe assessed outcome of patients with moderate and severe COVID-19 following treatment with convalescent plasma (CP) and the association with IgG levels in transfused CP.MethodsA prospective cohort study. Primary outcome was improvement at day 14 defined as alive, not on mechanical ventilation, and moderate, mild, or recovered from COVID-19. Antibody levels in CP units were unknown at the time of treatment. IgG against the spike protein S1 was subsequently measured by ELISA. Neutralizing antibodies titers were determined in a subset. Outcome was assessed in relation to the mean antibody level transfused to the patients (≤4.0 versus >4.0).FindingsOf 49 patients, 11 (22.4%) had moderate, 38 (77.6%) had severe disease, 28 were ventilated. At day 14, 24 (49.0%) patients improved, 9 (18.4%) died, and 13 (26.5%) were ventilated. In 14/98 (14.3%) CP units IgG was < 1.1 (cutoff calibration) and in 60 (61.2%) ≤4.0. IgG level and neutralizing antibody titer were correlated (0.85 p < 0.001). In patients receiving ≤4.0 antibody levels, 11/30 improved (36.7%) versus 13/19 (68.4%) in patients receiving >4.0 odds ratio (OR) 0.267 [95% confidence interval (CI) 0.079–0.905], P = 0.030. In patients diagnosed >10 days prior to treatment, 4/14 (22.4%) improved in the ≤4.0 antibody group, versus 6/7 (85.7%) in the >4.0 antibody group, OR 0.048 (95% CI, 0.004–0.520), P = 0.007. No serious adverse events were reported.InterpretationTreatment with CP with higher levels of IgG against S1 may benefit patients with moderate and severe COVID-19. IgG against S1 level in CP predicts neutralization antibodies titers.

Clinical Characteristics and Outcome of Hospitalized COVID-19 Patients in a MERS-CoV Endemic Area

BackgroundThe Kingdom of Saudi Arabia (KSA) reported 170,639 cases and 1430 deaths from COVID-19 since the first case emerged in the country on March 2 through June 25, 2020. The objective of this report is to describe the characteristics and outcome observed among 99 hospitalized COVID-19 patients in the largest academic hospital in KSA, and assess co-infection with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).MethodsThis single-center case series data included select epidemiological, clinical, radiological features and laboratory findings of all confirmed hospitalized cases of COVID-19 in King Saud University Medical City (KSUMC), Riyadh, KSA, from March 22 until May 31, 2020, followed through June 6, 2020. We conducted retrospective analysis of listed data from 99 hospitalized patients and present characteristics and factors associated with severity in percentages and univariate odds ratios. Cases were confirmed using nasopharyngeal or throat swab by real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and MERS-CoV by RT-PCR.ResultsThe 99 hospitalized COVID-19 patients included in this analysis constitute 16% of 632 positive SARS-CoV-2 among 6633 persons who were tested at the KSUMC (positivity rate, 9.4%). MERS-CoV PCR was negative in all 99 patients tested. The majority of these 99 hospitalized patients were males (66%), had a mean age of 44 years (range, 19–87), and a quarter (25.3%) were health care workers. Patients with comorbid conditions accounted for 52.5% of patients including the 8.1% who were asymptomatic; diabetes mellitus being the most frequent (31.3%), followed by hypertension (22.2%). The most common presenting symptoms were fever (67.7%), cough (60.6%), dyspnea (43.4%), upper respiratory symptoms (27.3%), fatigue (26.3%), diarrhea (19.2%) and loss of smell (9.1%). The clinical conditions among these 99 patients included upper respiratory tract infection (47.5%), abnormal chest X-ray, lymphopenia, high inflammatory markers a fifth (21%) of patients had moderate pneumonia, while 7% had severe pneumonia with 22.2% requiring admission to the intensive care unit and 12.1% died. Late presentation with severe disease, an abnormal chest X-ray, lymphopenia, high inflammatory markers (C-reactive protein, ferritin, and procalcitonin), and end organ damage (high creatinine or high aspartate aminotransferase) were predictors for admission to critical care unit or died.ConclusionWe observed no MERS-CoV co-infection in this early cohort of hospitalized COVID-19 patients who were relatively young, more than half had comorbid conditions, presented with fever and/or cough, an abnormal chest X-ray, lymphopenia, and high inflammatory markers. Given MERS-CoV endemicity in the country, co-monitoring of MERS-CoV and SARS-CoV-2 coinfection is critical.

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19

Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. ClinicalTrials.gov Identifier: NCT04292730.

Acute pancreatitis and nosocomial COVID-19: Cause specific host responses may determine lung injury

BackgroundCoronavirus disease 2019 (COVID-19) presents with myriad extra-pulmonary manifestation and a high mortality in patients with comorbidities. Its effect on patients with pre-existing acute pancreatitis is not known. MethodsWe hereby, present 3 cases with severe acute pancreatitis with persistent respiratory failure who acquired nosocomial COVID-19 during their hospital stay after recovery from respiratory failure. Their clinical course is highlighted which reflects on pathophysiology of organ dysfunction in these 2 disease states. ResultsNone of the 3 patients with severe acute pancreatitis who developed nosocomial COVID-19 redeveloped respiratory failure due to COVID-19 despite having recently recovered from pancreatitis induced acute hypoxemic respiratory failure. Only one patient developed SARS-CoV2 induced moderate pneumonia. ConclusionThese cases highlight that host responses and mechanisms of lung injury might be different in severe acute pancreatitis and COVID-19.

Low-dose subcutaneous tocilizumab to prevent disease progression in patients with moderate COVID-19 pneumonia and hyperinflammation

AimThis study aimed to evaluate the safety and efficacy profile of low-dose tocilizumab (TCZ), to prevent disease progression, subcutaneously administered to patients with moderate COVID-19 pneumonia and hyperinflammation. MethodsClinical characteristics and outcomes were retrospectively analysed of patients – with laboratory-confirmed bilateral COVID-19 pneumonia, hyperinflammation (C-reactive protein (CRP) ≥20 mg/dL), no hypoxaemia (oxygen saturation >90%), and no contraindications to TCZ – who were treated with subcutaneous TCZ (324 mg) administered within 48 h from hospitalization on top of standard of care (SOC). They were compared with matched controls treated with SOC only before TCZ was available at the institution. Clinical data were available for all patients until death or until day 35 for those discharged from hospital. FindingsTen consecutive patients (six males, median age 55 years) treated with TCZ on top of SOC, and ten patients (six males, median age 56 years) treated with SOC only were included. TCZ was well-tolerated with no clinically relevant adverse events. TCZ was associated with a reduction in CRP at day 1 (–50%, IQR –28 to –80) and day 3 (–89%, IQR –79 to –96; p = 0.005 for within-group), whereas there was no significant change in CRP values in the SOC group (p < 0.001 for between-group comparisons at both time points). TCZ resulted in a parallel improvement in oxygenation, as assessed by the ratio of partial pressure of oxygen to fraction of inspired oxygen (P/F) ratio, which increased at day 1 (+11%, IQR +6 to +16; p = 0.005 for within-group and p = 0.006 for between-group comparisons), and day 3 (+23%, IQR +16 to +34; p = 0.005 for within-group and p = 0.003 for between-group comparisons). None of the TCZ-treated patients had disease progression, defined as requirement of oxygen therapy or mechanical ventilation, whereas progression occurred in five (50%) patients among the SOC group. ConclusionsLow-dose subcutaneous TCZ may be a safe and promising therapeutic option administered on top of SOC to prevent disease progression in hospitalised patients with moderate COVID-19 and hyperinflammation.

Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.

Dynamic CT assessment of disease change and prognosis of patients with moderate COVID-19 pneumonia.

OBJECTIVES:To assess prognosis or dynamic change from initial diagnosis until recovery of the patients with moderate coronavirus disease (COVID-19) pneumonia using chest CT images.MATERIALS AND METHODS:In this retrospective study, 33 patients (18 men, 15 women; median age, 49.0 years) with confirmed with moderate COVID-19 pneumonia in a multicenter hospital were included. The patients underwent at least four chest non-contrast-enhanced computed tomography (CT) scans at approximately 5-day intervals. We analyzed the clinical and CT characteristics of the patients. Moreover, the total CT score and the sum of lung involvement were determined for every CT scan.RESULTS:The most widespread presenting symptoms were fever (32/33, 97.0%) and cough (17/33, 51.5%), which were often accompanied by decreased lymphocyte count (15/33, 45.5%) and increased C-reactive protein levels (18/33, 54.6%). Bilateral, multifocal ground glass opacities (32/33, 97.0%), consolidation (25/33, 75.8%), vascular thickening (23/33, 69.7%), and bronchial wall thickening (21/33, 63.6%) with peripheral distribution were the most frequent CT findings during moderate COVID-19 pneumonia. In patients recovering from moderate COVID-19 pneumonia, four stages (stages 1–4) of evolution were identified on chest CT with average CT scores of 3.4±2.3, 6.0±4.4, 5.6±3.8, and 4.9±3.2, respectively, from the onset of symptoms. For most patients, the peak of average total CT score increased for approximately 8 days after the onset of symptoms, after which it decreased gradually. The mean CT score of all patients was 4.7 at the time of discharge.CONCLUSION:The moderate COVID-19 pneumonia CT score increased rapidly in a short period of time initially, followed by a slow decline over a relatively long time. The peak of the course occurred in stage 2. Complete recovery of patients with moderate COVID-19 pneumonia with high mean CT score at the time of discharge requires longer time.

Characteristics of Venous Thromboembolism in COVID-19 Patients: A Multicenter Experience from Northern Italy

BackgroundThe liability of patients affected by novel coronavirus disease (COVID-19) to develop venous thromboembolic events is widely acknowledged. However, many particulars of the interactions between the two diseases are still unknown. This study aims to outline the main characteristics of deep venous thrombosis (DVT) and pulmonary embolism (PE) in COVID-19 patients, based on the experience of four high-volume COVID-19 hospitals in Northern Italy.MethodsAll cases of COVID-19 in-hospital patients undergoing duplex ultrasound (DUS) for clinically suspected DVT between March 1st and April 25th, 2020, were reviewed. Demographics and clinical data of all patients with confirmed DVT were recorded. Computed tomography pulmonary angiographies of the same population were also examined looking for signs of PE.ResultsOf 101 DUS performed, 42 were positive for DVT, 7 for superficial thrombophlebitis, and 24 for PE, 8 of which associated with a DVT. Most had a moderate (43.9%) or mild (16.9%) pneumonia. All venous districts were involved. Time of onset varied greatly, but diagnosis was more frequent in the first two weeks since in-hospital acceptance (73.8%).Most PEs involved the most distal pulmonary vessels, and two-thirds occurred in absence of a recognizable DVT.ConclusionsDVT, thrombophlebitis, and PE are different aspects of COVID-19 procoagulant activity and they can arise regardless of severity of respiratory impairment. All venous districts can be involved, including the pulmonary arteries, where the high number and distribution of the thrombotic lesions without signs of DVT could hint a primitive thrombosis rather than embolism.

COVID-19 in kidney transplant recipients: A multicenter experience in Istanbul.

IntroductionManagement of COVID‐19 in kidney transplant recipients should include treatment of the infection, regulation of immunosuppression, and supportive therapy. However, there is no consensus on this issue yet. This study aimed to our experiences with kidney transplant recipients diagnosed with COVID‐19.Material and MethodsKidney transplant recipients diagnosed with COVID‐19 from five major transplant centers in Istanbul, Turkey, were included in this retrospective cohort study. Patients were classified as having moderate or severe pneumonia for the analysis. The primary endpoint was all‐cause mortality. The secondary endpoints were acute kidney injury, the average length of hospital stay, admission to intensive care, and mechanical ventilation.ResultsForty patients were reviewed retrospectively over a follow‐up period of 32 days after being diagnosed with COVID‐19. Cough, fever, and dyspnea were the most frequent symptoms in all patients. The frequency of previous induction and rejection therapy was significantly higher in the group with severe pneumonia compared to the moderate pneumonia group. None of the patients using cyclosporine A developed severe pneumonia. Five patients died during follow‐up in the intensive care unit. None of the patients developed graft loss during follow‐up.DiscussionCOVID‐19 has been seen to more commonly cause moderate or severe pneumonia in kidney transplant recipients. Immunosuppression should be carefully reduced in these patients. Induction therapy with lymphocyte‐depleting agents should be carefully avoided in kidney transplant recipients during the pandemic period.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease.

SARS-CoV-2 Pandemic Response, Clinical Characteristics and Outcomes at Bangkok's Largest Emerging Diseases Clinical Centre

Background: The SARS-CoV2 pandemic has affected over 3 million people globally. As of 5 April 2020, 2,169 cases were reported in Thailand, with half occurring in Bangkok. Data on interventions to curb the spreading of Coronavirus Disease 2019 (COVID-19) in resource-limited settings are limited. Objectives: To describe the operational response, clinical spectrum and outcomes of COVID-19 at the Thai Red Cross-Emerging Infectious Diseases Clinical Centre (TRC-EID-CC), Bangkok’s largest EID Centre. Methods: A cohort study on COVID-19 patients was performed. Surge capacity preparations utilised healthcare teams for critical care patients in intensive care units, isolation wards for mild to severe cases and home care teams to discharge mild cases early to home isolation or modified hotels with telehealth monitoring. COVID-19 diagnoses were confirmed by reverse transcriptase polymerase chain reaction of SARS-CoV2 from throat and nasopharyngeal swab samples. Case severity was defined as mild, moderate (pneumonia), severe (pneumonia with hypoxaemia) and critical (mechanical ventilation required). Findings: From 15 January to 5 April 2020, 3,885 individuals were screened. Isolation ward capacity was increased by 500% from initial settings and a modified hotel capacity was added. Of the 158 COVID-19 confirmed cases, 63% were mild, 19% moderate, 12% severe and 6% critical. Factor associated with severe and critical cases were age > 45 years, male gender and lymphocyte count < 1.5 x109/L at presentation. All pneumonia cases with the exception of 3 received COVID-19 targeted treatments, 40 (74%) with favipiravir-based regimens and 14 (26%) with hydroxychloroquine and darunavir/ritonavir or azithromycin. Median length of stay was 5 days (IQR 3-10). As of 5 May 2020, 98% were discharged and 30-day mortality rate was zero. Interpretation: Prompt surge capacity planning, monitoring of progression to pneumonia by multidisciplinary teams allocated to patients by disease severity with rapid initiation of antiviral treatment and high quality respiratory care are important in achieving favourable programme outcomes. ​ Funding Statement: This study was supported by the Ratchadapiseksompoj Fund, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (RA (PO) 001/63). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Approval for this study was granted by the Faculty of Medicine, Chulalongkorn University (IRB 312/63). Written informed consent was waived by the Ethics Commission.

Non-Overt Coagulopathy in Non-ICU Patients with Mild to Moderate COVID-19 Pneumonia.

Introduction: Aim of the study is to assess the occurrence of early stage coagulopathy and disseminated intravascular coagulation (DIC) in patients with mild to moderate respiratory distress secondary to SARS-CoV-2 infection. Materials and methods: Data of patients hospitalized from 18 March 2020 to 20 April 2020 were retrospectively reviewed. Two scores for the screening of coagulopathy (SIC and non-overt DIC scores) were calculated. The occurrence of thrombotic complication, death, and worsening respiratory function requiring non-invasive ventilation (NIV) or admission to ICU were recorded, and these outcomes were correlated with the results of each score. Chi-square test, receiver-operating characteristic curve, and logistic regression analysis were used as appropriate. p Values < 0.05 were considered statistically significant. Results: Data of 32 patients were analyzed. Overt-DIC was diagnosed in two patients (6.2%), while 26 (81.2%) met the criteria for non-overt DIC. Non-overt DIC score values ≥4 significantly correlated with the need of NIV/ICU (p = 0.02) and with the occurrence of thrombotic complications (p = 0.04). A score ≥4 was the optimal cut-off value, performing better than SIC score (p = 0.0018). Values ≥4 in patients with thrombotic complications were predictive of death (p = 0.03). Conclusions: Overt DIC occurred in 6.2% of non-ICU patients hospitalized for a mild to moderate COVID-19 respiratory distress, while 81.2% fulfilled the criteria for non-overt DIC. The non-overt DIC score performed better than the SIC score in predicting the need of NIV/ICU and the occurrence of thrombotic complications, as well as in predicting mortality in patients with thrombotic complications, with a score ≥4 being detected as the optimal cut-off.

Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization

Background & AimsAlthough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus.MethodsWe performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2.ResultsPatients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients.ConclusionsIn a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.

COVID-19 pneumonia and pregnancy; a systematic review and meta-analysis

Background The new SARS-CoV-2 originated from Wuhan, China is spreading rapidly worldwide. A number of SARS-CoV-2 positive pregnant women have been reported. However, more information is still needed on the pregnancy outcome and the neonates regarding COVID-19 pneumonia. Material and Methods A systematic search was done and nine articles on COVID-19 pneumonia and SARS-CoV-2 positive pregnant women were extracted. Some maternal-fetal characteristics were extracted to be included in the meta-analysis. Results The present meta-analysis was conducted on 87 SARS-CoV-2 positive pregnant women. Almost 65% of the patients reported a history of exposure to an infected person, 78% suffered from mild or moderate COVID-19, 99.9% had successful termination, 86% had cough, and 68% had fever (p = .022 and p < .001). The overall proportions of vertical transmission, still birth, and neonatal death were zero, 0.002, and, 0.002, respectively (p = 1, p = .86, and p = .89, respectively). The means of the first- and fifth-minute Apgar scores were 8.86 and 9, respectively (p < .001 for both). The confounding role of history of underlying diseases with an estimated overall proportion of 33% (p = .03) resulted in further investigations due to sample size limitation. A natural history of COVID-19 pneumonia in the adult population was presented, as well. Conclusion Currently, no evidence of vertical transmission has been suggested at least in late pregnancy. No hazards have been detected for fetuses or neonates. Although pregnant women are at an immunosuppressive state due to the physiological changes during pregnancy, most patients suffered from mild or moderate COVID-19 pneumonia with no pregnancy loss, proposing a similar pattern of the clinical characteristics of COVID-19 pneumonia to that of other adult populations.