Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

Maternal and Perinatal Outcomes of Pregnant Patients with Coronavirus Disease 2019: Data from a University Hospital Setting in Tirana, Albania, May 2020 to November 2021.

Scientific evidence suggests an increased risk of maternal and obstetric complications in pregnant patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study is aimed at evaluating perinatal and maternal outcomes among patients with coronavirus disease 2019 (COVID-19) in a university hospital setting. This was a prospective cohort study of 177 pregnant women with confirmed SARS-CoV-2 infection at a tertiary hospital between May 2020 and November 2021. Both symptomatic and asymptomatic women with a positive reverse transcription-polymerase chain reaction test result at any time during pregnancy were included in this study. For the purpose of this study, we classified COVID-19 cases into two groups: mild and severe cases. The two groups were then compared to predict how the clinical presentation of COVID-19 affected adverse maternal and perinatal outcomes. Gestational age ≥ 20 weeks at the time of infection was significantly associated with the occurrence of severe forms of the disease (relative risk (RR) 3.98, p = 0.01). Cesarean section was the preferred mode of delivery, with 95 women (62.1%) undergoing surgery. A total of 149 neonates were delivered to women who had confirmed SARS-CoV-2 infection at any time during the course of pregnancy of which thirty-five (23.5%) were admitted to the neonatal intensive care unit (NICU). Severe forms of COVID-19 increased the risk of premature delivery (RR 6.69, p < 0.001), emergency cesarean delivery (RR 9.4, p < 0.001), intensive care hospitalization (RR 51, p < 0.001), and maternal death (RR 12.3, p = 0.02). However, severe forms of SARS-CoV-2 infection are not directly responsible for low birth weight or the need for neonatal resuscitation. Our findings suggest that pregnant women presenting with severe COVID-19 disease are at an increased risk of adverse maternal and perinatal outcomes, such as premature delivery, cesarean section, admission to the ICU, and maternal death. Infection after the 20th week of gestation increases the risk of developing severe forms of the disease.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Cytokines as biomarkers of Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a potentially severe disease caused by CCHF virus. As in other viral hemorrhagic fevers, it is considered that the course and outcome of the disease depend on the viral load and the balance among the immune response mediators, and that a fatal outcome is the result of a "cytokine storm." The level of 27 cytokines was measured in serum samples taken from 29 patients during the acute phase of the disease. Two cases were fatal. Among survivors, significant differences between severe and non-severe cases were observed in the levels of IP-10, and MCP-1, while the levels of IL-1b, IL-5, IL-6, IL-8, IL-9, IL-10, IL-15, IP-10, MCP-1, TNF-α, and RANTES differed significantly between fatal and non-fatal cases (P < 0.05). RANTES was negatively correlated with the outcome of the disease. A striking similarity with the cytokine patterns seen in Ebola virus disease was observed. A weak Th1 immune response was seen. The viral load was positively correlated with IL-10, IP-10, and MCP-1 levels, and negatively correlated with the ratio IL-12/IL-10. Especially IP-10 and MCP-1 were significantly associated with the viral load, the severity and outcome of the disease, and they could act as biomarkers and, probably, as potential targets for treatment strategies design.

Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.

Severity and Mortality Predictors of COVID-19 Patients with Thrombotic Events-Evidence from the "COVID-One" Hospital in Albania.

COVID-19 vaccination leads to lower infection, morbidity, and mortality rates. However, COVID-19 infection leads to the development of coagulopathy-related manifestations in the form of both venous and arterial thromboembolism. This study aimed to assess the severity and mortality predictors of COVID-19 patients with thrombotic events in hospitalized patients in Albania. This is a retrospective study conducted in the "Mother Tereza" University Hospital of Tirana. Data were retrieved from the electronic databases of the hospital and only COVID-19 cases admitted to the infectious department during August−December 2020 were selected. Patients who, at admission, had a C-reactive protein (CRP) (mg/L) more than double and a D-dimer (ng/mL) more than triple according to international standards were included in the study. We performed univariate and multivariable logistic regression analysis, calculating unadjusted and adjusted odds ratios (ORs). A p-value < 0.05 was considered statistically significant. The study population included 60 hospitalized persons with a mean age of 64.4 years. Increased lactate dehydrogenase (LDH) (OR = 2.93; 95% CI = 0.82−10.42, p-value = 0.1) and increased creatine kinase (CK) (OR = 2.17; 95% CI = 0.63−7.46, p-value = 0.22) were related with increased probability of death. Moreover, a decreased number of lymphocytes was associated with increased mortality but with no statistical significance (OR = 0.40; 95% CI = 0.11−1.40, p-value = 0.15). The survival rate was higher for patients without comorbidities (p = 0.045). These results could serve as a baseline and as a reference for healthcare personnel who provides services to hospitalized patients with COVID-19. Further studies should take into consideration the vaccination of the population as well as including more hospitals and patients.

Severe hypocalcaemia in a COVID-19 female patient.

SUMMARY: Comorbidities are a risk factor for patients with COVID-19 and the mechanisms of disease remain unclear. The aim of this paper is to present a case report of an COVID-19 patient with severe hypocalcaemia. This is a report of an 81-year-old female, suffered from myalgia and fatigue for more than 3-4 weeks. Fever and cough appear 2 days before she presented to the emergency room. On physical examination, she was febrile with a temperature of 38.8°C, accompanied by cough, sore throat, headache, fatigue, and muscle ache. Her past medical history was remarkable with no chronic disease. She had lymphopenia. Laboratory test revealed moderate liver dysfunction, hypoalbuminemia, and severe hypocalcaemia (serum corrected calcium level: 5.7 mg/dL). Parathyroid hormone (PTH) was 107.9 pg/mL (range: 15-65) and 25(OH)2D levels was 4.5 ng/mL (range: 25-80). Chest CT scan detected peripheral ground-glass opacity. Throat swab for coronavirus by RT-PCR assay tested positive for the virus. She was treated with lopinavir/ritonavir, third generation cephalosporin, anticoagulant, daily high-dose calcium acetate, vitamin D3, fresh frozen plasma and oxygen therapy. She was discharged after two negative throat swab tests for coronavirus by conventional RT-PCR. LEARNING POINTS: Comorbidities are a risk factor for patients with COVID-19. Laboratory findings are unspecific in COVID-19 patients; laboratory abnormalities include lymphopenia, elevated of LDH, CPK and the inflammatory markers, such as C reactive protein, ferritinemia and the erythrocyte sedimentation rate. In addition to inflammatory markers, in COVID-19 patients it is crucial to check the level of vitamin D and calcium. There may be a correlation between vitamin D deficiency and the severity of COVID-19 disease.

Risk factors for poor outcome of patients with Coronavirus disease 2019 (COVID-19) in Albania.

INTRODUCTION: The study aims to identify potential risk factors for the poor outcome of hospitalized patients with SARS-CoV-2 infection in Albania. METHODOLOGY: A retrospective observational study on 133 consecutive hospitalized patients at "COVID 1" Hospital, University Hospital Center of Tirana. The study analyzed the correlation between potential risk factors and in-hospital mortality. RESULTS: The study included 133 patients, 65.4% of the patients were male, age 60.46 ± 13.53 years. The mortality rate resulted in 22.6%. Univariate analysis revealed that early risk factors for mortality included: laboratory alterations on admission, such as lymphocytes count < 1.000/mm3 (OR = 3.30, 95% CI = 1.17-9.33), lactate dehydrogenase > 250 U/L (OR = 12.48, 95% CI = 1.62-95.78) and D dimer > 2 mg/L (OR = 4.72, 95% CI = 1.96-11.36); lung parenchymal involvement > 75% on chest computed tomography on admission (OR = 54.00, 95% CI = 11.89 - 245.11). Cox proportional hazard regression showed that independent risk factors for mortality were lung parenchymal involvement > 75% on chest computed tomography (HR = 8.31, 95%CI: 1.62-42.45) and occurrence of complications during hospital stay (OR = 10.28, 95% CI = 2.02-52.33). CONCLUSIONS: The risk of poor outcome can be predicted from the early stage of COVID 19 disease, using laboratory data and chest computed tomography. Among patients with COVID 19, lung parenchymal involvement and alterations > 75% on chest computed tomography on admission and laboratory findings, such as lymphocytopenia, and elevated lactate dehydrogenase and D dimer levels, turned out to be early risk factors for in-hospital mortality.

A case with high bilirubinemia and hemolytic anemia during leptospirosis and a short review of similar cases.

BACKGROUND: Leptospirosis is characterized by very diverse clinical manifestations, which may range from flu-like subclinical forms to very severe presentations characterized by multi-organ failure, or to atypical presentations. One of its most aggressive presentations is Weil's disease, characterized by jaundice, hemorrhagic phenomena and renal failure. Cases with high bilirubinemia over 30mg/dL are not communes in human leptospirosis. Our aims are to present an atypical case presentation of human leptospirosis, characterized by jaundice and hemolytic anemia, and to make a short review in PubMed for similar cases. At the same time we want to emphasize the diversity of the clinical presentation of human leptospirosis. METHODS: A 54-year-old man presents at the emergency department of the infectious medicine with severe fatigue, nausea, vomiting, and generalized weakness. On exam, he was alert and well oriented; blood pressure was 80/50 mmHg and icteric. First blood examinations confirmed high bilirubinemia, thrombocytopenia and acute renal failure. RESULTS: Based on anamnestic and clinical evaluations, blood and serology examinations, the patient resulted with leptospirosis. The bilirubin reached 73.4mg/dL. At the same time on PubMed research we found only limited cases with leptospirosis associated with bilirubinemia over 30mg/dL and over less with hemolytic anemia. CONCLUSION: Based on our clinical experience, as well as literature data, we suggest that clinicians should have a high index of suspicion in cases of jaundice with exposure possibilities for infectious diseases. Connection of high bilirubinemi over then 30mg/dL and hemolytic anemia in human leptospirosis is an unical case report.

Crimean-Congo hemorrhagic fever with hepatic impairment and vaginal hemorrhage: a case report.

BACKGROUND: Crimean-Congo hemorrhagic fever is a tick-borne disease described in more than 30 countries in Europe, Asia, and Africa. Albania is located in the southwestern part of the Balkan Peninsula. In 1986, the first case of Crimean-Congo hemorrhagic fever was registered, and cases of patients with hemorrhagic fever are rising, and most of them present in a serious condition, when the mortality rate is very high. In districts like Mirdite, Lezhe, Gjirokaster, Skrapar, Erseke, and Kukes, there is delineated human-to-human transmission. CASE PRESENTATION: We report the case of a 32 year-old Albanian woman from a rural area of Albania. She was hospitalized at the Infectious Diseases Service, for a severe influenza-like illness of 4 days duration. Our patient had been bitten by a tick while working in her garden. She presented with nausea, vomiting, headache and muscle pain. A physical examination found a high fever of 40 °C, an enlarged liver, petechia, and vaginal bleeding; flapping tremor and fetor hepaticus were found as a sign for hepatic encephalopathy; and confusion and disorientation were observed in her neurological examination. Her platelet and white blood cell counts were very low, while her aspartate aminotransferase and alanine aminotransferase levels were very high. She was transferred to the intensive care unit because of her worsening condition. Serological and C-reactive protein test results for Crimean-Congo hemorrhagic fever were positive. She was treated with oral ribavirin and discharged with normal parameters. CONCLUSIONS: People in high-risk professions in the endemic areas should be informed and trained on the risk of Crimean-Congo hemorrhagic fever as a matter of urgency. Vaginal bleeding is not always a gynecological problem. In Albania, these places are the mountainous areas, so people who have traveled to these areas and who have symptoms after a tick bite are advised to contact their doctors.

Epidemiological, clinical and therapeutic aspects of cerebral malaria imported in Albania.

This is a case-report of two patients with cerebral malaria (CM) imported from West-African countries. Notably, this form of malaria was developed as a second disease episode, while the first episode was experienced in West Africa. These findings suggest that the second episode of malaria was caused by a different strain of Plasmodium falciparum as compared to the first one. They are the first cerebral malaria cases imported in Albania after the eradication and absence of Plasmodium for five decades. Early treatment of cerebral malaria is decisive on the duration of coma and disease's outcome.