Background The COVID-19 pandemic, caused by severe acute respi ratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respi ratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare.Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerg ing as an important complication, with cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin.Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish nonspecific complications of severe disease (eg, hypoxic encephalo pathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

Background The COVID-19 pandemic, caused by severe acute respi ratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respi ratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare.Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerg ing as an important complication, with cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin.Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish nonspecific complications of severe disease (eg, hypoxic encephalo pathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

Background A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes. Methods For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 10 9 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3–6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis. Findings Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32–55) was lower than in the non-VITT group (57 years; 41–62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2–4) than non-VITT patients (two, 2–3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55...

Analysis 3.3. Comparison 3: HCQ + azithromycin versus standard care for treatment, Outcome 3: Length of hospital stay in days...

Background The coronavirus disease 2019 (COVID‐19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. Objectives To evaluate the effects of chloroquine (CQ) or hydroxychloroquine (HCQ) for 1) treating people with COVID‐19 on death and time to clearance of the virus; 2) preventing infection in people at risk of SARS‐CoV‐2 exposure; 3) preventing infection in people exposed to SARS‐CoV‐2. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Current Controlled Trials (www.controlled‐trials.com), and the COVID‐19‐specific resources www.covid‐nma.com and covid‐19.cochrane.org, for studies of any publication status and in any language. We performed all searches up to 15 September 2020. We contacted researchers to identify unpublished and ongoing studies. Selection criteria We included randomized controlled trials (RCTs) testing chloroquine or hydroxychloroquine in people with COVID‐19, people at risk of COVID‐19 exposure, and people exposed to COVID‐19. Adverse events (any, serious, and QT‐interval prolongation on electrocardiogram) were also extracted. Data collection and analysis Two review authors independently assessed eligibility of search results, extracted data from the included studies, and assessed risk of bias using the Cochrane ‘Risk of bias’ tool. We contacted study authors for clarification and additional data for some studies. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). We performed meta‐analysis using a random‐effects model for outcomes where pooling of effect estimates was appropriate. Main results 1. Treatment of COVID‐19 disease We included 12 trials involving 8569 participants, all of whom were adults. Studies were from China (4); Brazil, Egypt, Iran, Spain, Taiwan, the UK, and North America (each 1 study); and a global study in 30 countries (1 study). Nine were in hospitalized patients, and three from ambulatory care. Disease severity, prevalence of comorbidities, and use of co‐interventions varied substantially between trials. We found potential risks of bias across all domains for several trials. Nine trials compared HCQ with standard care (7779 participants), and one compared HCQ with placebo (491 participants); dosing schedules varied. HCQ makes little or no difference to death due to any cause (RR 1.09, 95% CI 0.99 to 1.19; 8208 participants; 9 trials; high‐certainty evidence). A sensitivity analysis using modified intention‐to‐treat results from three trials did not influence the pooled effect e...

VDR gene polymorphisms and hypovitaminosis D may predispose to MDR-TB. Lower serum 25(OH)D may increase time to MDR-TB sputum smear negativity.

No abstract

BackgroundLinezolid was recently re‐classified as a Group A drug by the World Health Organization (WHO) for treatment of multi‐drug resistant tuberculosis (MDR‐TB) and extensively drug‐resistant tuberculosis (XDR‐TB), suggesting that it should be included in the regimen for all patients unless contraindicated. Linezolid use carries a considerable risk of toxicity, with the optimal dose and duration remaining unclear. Current guidelines are mainly based on evidence from observational non‐comparative studies.ObjectivesTo assess the efficacy of linezolid when used as part of a second‐line regimen for treating people with MDR and XDR pulmonary tuberculosis, and to assess the prevalence and severity of adverse events associated with linezolid use in this patient group.Search methodsWe searched the following databases: the Cochrane Infectious Diseases Specialized Register; CENTRAL; MEDLINE; Embase; and LILACS up to 13 July 2018. We also checked article reference lists and contacted researchers in the field.Selection criteriaWe included studies in which some participants received linezolid, and others did not. We included randomized controlled trials (RCTs) of linezolid for MDR and XDR pulmonary tuberculosis to evaluate efficacy outcomes. We added non‐randomized cohort studies to evaluate adverse events.Primary outcomes were all‐cause and tuberculosis‐associated death, treatment failure, and cure. Secondary outcomes were treatment interrupted, treatment completed, and time to sputum culture conversion. We recorded frequency of all and serious adverse events, adverse events leading to drug discontinuation or dose reduction, and adverse events attributed to linezolid, particularly neuropathy, anaemia, and thrombocytopenia.Data collection and analysisTwo review authors (BS and DC) independently assessed the search results for eligibility and extracted data from included studies. All review authors assessed risk of bias using the Cochrane ‘Risk of bias' tool for RCTs and the ROBINS‐I tool for non‐randomized studies. We contacted study authors for clarification and additional data when necessary.We were unable to perform a meta‐analysis as one of the RCTs adopted a study design where participants in the study group received linezolid immediately and participants in the control group received linezolid after two months, and therefore there were no comparable data from this trial. We deemed meta‐analysis of non‐randomized study data inappropriate.Main resultsWe identified three RCTs for inclusion. One of these studies had serious problems with allocation of the study drug and placebo, so we could not analyse data for intervention effect from it. The remaining two RCTs recruited 104 participants. One randomized 65 participants to receive linezolid or not, in addition to a background regimen; the other randomized 39 participants to addition of linezolid to a background regimen immediately, or after a delay of two months. We included 14 non‐randomized cohort studies (two prospective, 12 retrospective), with a total of 1678 partici...