Omicron variant of SARS-CoV-2 exhibits an increased resilience to the antiviral type I interferon response.

The new variant of concern (VOC) of SARS-CoV-2, Omicron (B.1.1.529), is genetically very different from other VOCs. We compared Omicron with the preceding VOC Delta (B.1.617.2) and the wildtype (wt) strain (B.1) with respect to their interactions with the antiviral interferon (IFN-alpha/beta) response in infected cells. Our data indicate that IFN induction by Omicron is low and comparable to the wt, whereas Delta showed an increased IFN induction. However, Omicron exceeded both the wt and the Delta strain with respect to the ability to withstand the antiviral state imposed by IFN-alpha.

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results.

BACKGROUND: The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS: An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS: In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS: Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION: BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS).

Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

INTRODUCTION: Vidofludimus calcium has shown anti-inflammatory effects in clinical trials of autoimmune diseases and recently demonstrated antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a double-blind, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy of vidofludimus calcium in patients hospitalized for coronavirus disease 2019 (COVID-19) in Europe and the USA. METHODS: Patients aged 18 years or older who positive for COVID-19 were randomized (1:1) to receive placebo or 45 mg vidofludimus calcium for 14 days with both groups receiving standard-of-care treatment. The primary endpoint was the need for invasive ventilation after 28 days (ClinicalTrials.gov NCT04379271; EudraCT 2020-001264-28). RESULTS: Between June 12, 2020 and December 10, 2020, a total of 223 were randomized to receive either placebo (n = 112) or vidofludimus calcium (n = 111); three patients withdrew consent and were not treated. Eight (9%) patients in the placebo group and 12 (11%) patients in the vidofludimus calcium group needed invasive ventilation during the 28-day study period, which was lower than the assumed rate of 40%. Time to clinical improvement was shorter by approximately 1 day in the vidofludimus calcium group (15.0 days [90% CI 14.8-15.9]) compared to the placebo group (15.9 days [90% CI 14.9-19.9]). This effect was greatest in patients who initiated therapy within 9 days of symptom onset (3.8 days shorter in the vidofludimus calcium group). Higher trough concentrations of vidofludimus calcium were associated with quicker time to clinical recovery. The rate and timing of appearance of anti-SARS-CoV-2 antibodies were not different between groups. Serious adverse events occurred in 4 (4%) patients in the placebo group and 2 (2%) patients in the vidofludimus calcium group; treatment-emergent adverse events of increased severity related to COVID-19 occurred in 13 (12%) patients in the placebo group and 8 (7%) patients in the vidofludimus calcium group. Overall mortality was low (2%). CONCLUSIONS: These findings support vidofludimus calcium being safe and well tolerated in patients with COVID-19.

Online consultations in mental healthcare: Modelling determinants of use and experience based on an international survey study at the onset of the pandemic.

Introduction: While online consultations have shown promise to be a means for the effective delivery of high-quality mental healthcare and the first implementations of these digital therapeutic contacts go back nearly two decades, uptake has remained limited over the years. The onset of the COVID-19 pandemic dramatically altered this relative standstill and created a unique turning point, with a massive amount of both professionals and clients having first hands-on experiences with technology in mental healthcare. Objective: The current study aimed to document the uptake of online consultations and explore if specific characteristics of mental health professionals across and beyond Europe could predict this. Methods: An international survey was designed to assess mental health professionals' (initial) experiences with online consultations at the onset of the pandemic: their willingness to make use of them and their prior and current experiences, alongside several personal characteristics. Logistic mixed-effects models were used to identify predictors of the use of online consultations, personal experience with this modality, and the sense of telepresence. Results: A total of 9115 healthcare professionals from 73 countries participated of which about two-thirds used online consultations during the initial COVID-19 outbreak. The current study identifies multiple determinants relating to the use and experience of online consultations, including the professionals' age, experience with the technology before the outbreak, the professional context, and training. Conclusions: Despite strong evidence supporting the relevance of training in digital mental health, this is clearly still lacking. Nevertheless, the COVID-19 pandemic presented a first, and potentially transformative, experience with online consultations for many healthcare professionals. The insights from this study can help support professionals and, importantly, (mental) healthcare organisations to create optimal circumstances for selective and high-quality continued use of online consultations.

The influence of face masks on speech intelligibility of cochlear implant users

Hearing impaired listeners heavily rely on facial expressions and unfiltered speech signals for a sufficient speech understanding. Due to the current Cov-id-19 pandemic face masks are worn by almost everyone every day. They therefore interfere especially with the communication of hearing impaired listeners. We used a modified audiovisual German matrix sentence test (AV-OLSA) 1 to further evaluate the effect of face masks on speech intelligibility in a cohort of cochlear implant users (CI, n = 15) and a control group of normal hearing listeners (NH, n = 5). Besides “audio-only”, “visual-only” and “audiovisual” conditions, we added modified conditions. These consisted of an audiovisual condition with a simulated mask and an audio signal, which was edited according to the acoustic filter properties of different face masks (surgical and FFP-2). Our preliminary data show a gain of 5.3 dB (CI) and 2.6 dB (NH) in speech reception thresholds at 80 % word recognition (SRT80%) respectively, if a speaker's video is added to an unfiltered audio signal. Different types of face masks (surgical and FFP-2) led to a deterioration in SRT80% in both groups of up to 7.6 dB (CI) and 4.2 dB (NH) when compared to an unfiltered audiovisual condition without a face mask. The acoustic filter properties of the face masks accounted for up to 2.2 dB (CI) and 1.5 dB (NH) of the deterioration in SRT80%. This effect was therefore less distinct compared to the effect of a missing video signal. Face masks complicate the daily communication. These effects are already detectable in a cohort of normal hearing listeners 2 and even more pronounced in hearing impaired listeners, e.g. cochlear implant users.

The ratio of serum LL-37 levels to blood leucocyte count correlates with COVID-19 severity.

Beneficial effects of vitamin D on COVID-19 progression have been discussed in several studies. Vitamin D stimulates the expression of the antimicrobial peptide LL-37, and evidence shows that LL-37 can antagonize SARS-CoV-2. Therefore, we investigated the association between LL-37 and vitamin D serum levels and the severity of COVID-19. To this end, 78 COVID-19 patients were divided into 5 groups according to disease severity. We determined serum levels of LL-37, vitamin D, and routine laboratory parameters. We demonstrated a correlation of CRP, IL-6, PCT, leukocyte count, and LDH with the severity of COVID-19. Our study did not demonstrate a direct relationship between serum levels of LL-37 and vitamin D and the severity of COVID-19. LL-37 is produced by granulocytes and released at the site of inflammation. Therefore, the analysis of LL-37 in broncho-alvelolar lavage rather than in patient serum seems critical. However, since LL-37 is produced by granulocytes, we determined serum LL-37 levels as a function of leukocyte count. The LL-37/leukocyte count ratio correlates highly significantly inversely proportional with COVID-19 severity. Our results indicate that the LL-37/leukocyte count ratio could be used to assess the risk of COVID-19 progression as early as hospital admission.

The impact of COVID-19 on medical students' practical skills and hygiene behavior regarding venipuncture: a case control study.

BACKGROUND: Despite their importance to current and future patient care, medical students' hygiene behaviors and acquisition of practical skills have rarely been studied in previous observational study. Thus, the aim of this study was to investigate the potential impact of the COVID-19 pandemic on medical student's hygiene and practical skills. METHODS: This case-control study assessed the effect of the COVID-19 pandemic on hygiene behavior by contrasting the practical skills and hygiene adherence of 371 medical students post the pandemic associated lockdown in March 2020 with that of 355 medical students prior to the SARS-CoV-2 outbreak. Students' skills were assessed using an objective structured clinical examination (OSCE). Their skills were then compared based on their results in hygienic venipuncture and the total OSCE score. RESULTS: During the SARS-CoV-2 pandemic, medical students demonstrated an increased level of compliance regarding hand hygiene before (prior COVID-19: 83.7%; during COVID-19: 94.9%; p < 0.001) and after patient contact (prior COVID-19: 19.4%; during COVID-19: 57.2%; p = 0.000) as well as disinfecting the puncture site correctly (prior COVID-19: 83.4%; during COVID-19: 92.7%; p < 0.001). Prior to the pandemic, students were more proficient in practical skills, such as initial venipuncture (prior COVID-19: 47.6%; during COVID-19: 38%; p < 0.041), patient communication (prior COVID-19: 85.9%; during COVID-19: 74.1%; p < 0.001) and structuring their work process (prior COVID-19: 74.4%; during COVID-19: 67.4%; p < 0.024). CONCLUSION: Overall, the COVID-19 pandemic sensitized medical students' attention and adherence to hygiene requirements, while simultaneously reducing the amount of practice opportunities, thus negatively affecting their practical skills. The latter development may have to be addressed by providing additional practice opportunities for students as soon as the pandemic situation allows.

Outpatient Pulmonary Rehabilitation in Patients with Long COVID Improves Exercise Capacity, Functional Status, Dyspnea, Fatigue, and Quality of Life.

BACKGROUND: COVID-19 survivors face the risk of long-term sequelae including fatigue, breathlessness, and functional limitations. Pulmonary rehabilitation has been recommended, although formal studies quantifying the effect of rehabilitation in COVID-19 patients are lacking. METHODS: We conducted a prospective observational cohort study including consecutive patients admitted to an outpatient pulmonary rehabilitation center due to persistent symptoms after COVID-19. The primary endpoint was change in 6-min walk distance (6MWD) after undergoing a 6-week interdisciplinary individualized pulmonary rehabilitation program. Secondary endpoints included change in the post-COVID-19 functional status (PCFS) scale, Borg dyspnea scale, Fatigue Assessment Scale, and quality of life. Further, changes in pulmonary function tests were explored. RESULTS: Of 64 patients undergoing rehabilitation, 58 patients (mean age 47 years, 43% women, 38% severe/critical COVID-19) were included in the per-protocol-analysis. At baseline (i.e., in mean 4.4 months after infection onset), mean 6MWD was 584.1 m (±95.0), and functional impairment was graded in median at 2 (IQR, 2-3) on the PCFS. On average, patients improved their 6MWD by 62.9 m (±48.2, p < 0.001) and reported an improvement of 1 grade on the PCFS scale. Accordingly, we observed significant improvements across secondary endpoints including presence of dyspnea (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Also, pulmonary function parameters (forced expiratory volume in 1 s, lung diffusion capacity, inspiratory muscle pressure) significantly increased during rehabilitation. CONCLUSION: In patients with long COVID, exercise capacity, functional status, dyspnea, fatigue, and quality of life improved after 6 weeks of personalized interdisciplinary pulmonary rehabilitation. Future studies are needed to establish the optimal protocol, duration, and long-term benefits as well as cost-effectiveness of rehabilitation.

Omicron variant of SARS-CoV-2 exhibits an increased resilience to the antiviral type I interferon response (preprint)

The new variant of concern (VOC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Omicron (B.1.1.529), is genetically very different from other VOCs. We compared Omicron with the preceding VOC Delta (B.1.617.2) and the wildtype strain (B.1) with respect to their interactions with the antiviral type I interferon (IFN-alpha/beta) response in infected cells. Our data indicate that Omicron has gained an elevated capability to suppress IFN induction upon infection and to better withstand the antiviral state imposed by exogenously added IFN-alpha.

Changes in Stroke Rehabilitation during the Sars-Cov-2 Shutdown in Switzerland.

INTRODUCTION: Many stroke survivors require continuous outpatient rehabilitation therapy to maintain or improve their neurological functioning, independ-ence, and quality of life. In Switzerland and many other countries, the shutdown to contain SARS-CoV-2 infections led to mobility restrictions and a decrease in therapy delivery. This study investigated the impact of the COVID-19 shutdown on stroke survivors' access to therapy, physical activity, functioning and mood. METHODS: A prospective observational cohort study in stroke subjects. At 4 time-points (before, during, after the shutdown, and at 3-month follow-up), the amount of therapy, physical activities, motor func-tion, anxiety, and depression were assessed. RESULTS: Thirty-six community-dwelling stroke subjects (median 70 years of age, 10 months post--stroke) were enrolled. Therapy reductions related to the shutdown were reported in 72% of subjects. This decrease was associated with significantly extended sedentary time and minimal deterioration in physical activity during the shutdown. Both parameters improved between reopening and 3-month follow-up. Depressive symptoms increased slightly during the observation period. Patients more frequently report-ed on self-directed training during shutdown. CONCLUSION: The COVID-19 shutdown had measurable immediate, but no persistent, effects on post--stroke outcomes, except for depression. Importantly, a 2-month reduction in therapy may trigger improvements when therapy is fully re-initiated thereafter.

Association of the COVID-19 outbreak with acute stroke care in Switzerland.

BACKGROUND AND PURPOSE: In Switzerland, the COVID-19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020. METHODS: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3-month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019. RESULTS: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13-April 26 of the years 2018-2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07). CONCLUSIONS: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained.

Ischemic stroke in COVID-19 patients: Mechanisms, treatment, and outcomes in a consecutive Swiss Stroke Registry analysis.

BACKGROUND: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. METHODS: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. RESULTS: Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). CONCLUSIONS: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.

Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis.

BACKGROUND: Headache is a frequent symptom following COVID-19 immunization with a typical onset within days post-vaccination. Cases of cerebral venous thrombosis (CVT) have been reported in adenovirus vector-based COVID-19 vaccine recipients. FINDINGS: We reviewed all vaccine related CVT published cases by April 30, 2021. We assessed demographic, clinical variables and the interval between the vaccination and onset of headache. We assessed whether the presence of headache was associated with higher probability of death or intracranial hemorrhage. We identified 77 cases of CVT after COVID-19 vaccination. Patients' age was below 60 years in 74/77 (95.8%) cases and 61/68 (89.7%) were women. Headache was described in 38/77 (49.4%) cases, and in 35/38 (92.1%) was associated with other symptoms. Multiple organ thrombosis was reported in 19/77 (24.7%) cases, intracranial hemorrhage in 33/77 (42.9%) cases and 19/77 (24.7%) patients died. The median time between vaccination and CVT-related headache onset was 8 (interquartile range 7.0-9.7) days. The presence of headache was associated with a higher odd of intracranial hemorrhage (OR 7.4; 95% CI: 2.7-20.8, p < 0.001), but not with death (OR: 0.51, 95% CI: 0.18-1.47, p = 0.213). CONCLUSION: Delayed onset of headache following an adenovirus vector-based COVID-19 vaccine is associated with development of CVT. Patients with new-onset headache, 1 week after vaccination with an adenovirus vector-based vaccine, should receive a thorough clinical evaluation and CVT must be ruled out.

Pulmonary rehabilitation in long COVID: more than just natural recovery!?

In the light of missing randomised controlled trials, some arguments suggest that pulmonary rehabilitation has beneficial effects beyond natural recovery https://bit.ly/3ze2xvw.

Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut.

Exacerbated pro-inflammatory immune response contributes to COVID-19 pathology. However, despite the mounting evidence about SARS-CoV-2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single-cell transcriptomics of SARS-CoV-2-infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target of SARS-CoV-2 and, interestingly, found the lack of positive correlation between susceptibility to infection and the expression of ACE2. Infected cells activated strong pro-inflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon. These findings reveal that SARS-CoV-2 curtails the immune response and highlights the gut as a pro-inflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.

Analysis of IgM, IgA, and IgG isotype antibodies Directed against SARS-CoV-2 spike glycoprotein and ORF8 in the course of COVID-19.

Immunoassays are a standard diagnostic tool that assesses immunity in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. However, immunoassays do not provide information about contaminating antigens or cross-reactions and might exhibit inaccurately high sensitivity and low specificity. We aimed to gain insight into the serological immune response of SARS-CoV-2 patients by immunoblot analysis. We analyzed serum immunoglobulins IgM, -A, and -G directed against SARS-CoV-2 proteins by immunoblot analysis from 12 infected patients. We determined IgG isotype antibodies by commercially available ELISA and assessed the clinical parameters of inflammation status and kidney and liver injury. Unexpectedly, we found no correlation between the presence of antibodies and the future course of the disease. However, attention should be paid to the parameters CRP, IL-6, and LDH. We found evidence of antibody cross-reactivity, which questions the reliability of results for serum samples that tested negative for anti-SARS-CoV-2 antibodies when assessed by immunoassays. Nevertheless, for the detection of IgG anti-SARS-CoV-2 antibodies, our data suggest that the use of the spike glycoprotein in immunoassays should be sufficient to identify positive patients. Using a combination of the spike glycoprotein and the open reading frame 8 protein could prove to be the best way of detecting anti-SARS-CoV-2 IgM antibodies.

Benefits of pulmonary rehabilitation in COVID-19: a prospective observational cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can result in a large variety of chronic health issues such as impaired lung function, reduced exercise performance and diminished quality of life. Our study aimed to investigate the efficacy, feasibility and safety of pulmonary rehabilitation in COVID-19 patients and to compare outcomes between patients with a mild/moderate and a severe/critical course of the disease. METHODS: Patients in the post-acute phase of a mild to critical course of COVID-19 admitted to a comprehensive 3-week inpatient pulmonary rehabilitation programme were included in this prospective, observational cohort study. Several measures of exercise performance (6-min walk distance (6MWD)), lung function (forced vital capacity (FVC)) and quality of life (36-question short-form health survey (SF-36)) were assessed before and after pulmonary rehabilitation. RESULTS: 50 patients were included in the study (24 with mild/moderate and 26 with severe/critical COVID-19). On admission, patients had a reduced 6MWD (mild: median 509 m, interquartile range (IQR) 426-539 m; severe: 344 m, 244-392 m), an impaired FVC (mild: 80%, 59-91%; severe: 75%, 60-91%) and a low SF-36 mental health score (mild: 49 points, 37-54 points; severe: 39 points, 30-53 points). Patients attended a median (IQR) 100% (94-100%) of all provided pulmonary rehabilitation sessions. At discharge, patients in both subgroups improved in 6MWD (mild/moderate: +48 m, 35-113 m; severe/critical: +124 m, 75-145 m; both p<0.001), FVC (mild/moderate: +7.7%, 1.0-17.8%, p=0.002; severe/critical: +11.3%, 1.0-16.9%, p<0.001) and SF-36 mental component (mild/moderate: +5.6 points, 1.4-9.2 points, p=0.071; severe/critical: +14.4 points, -0.6-24.5, p<0.001). No adverse event was observed. CONCLUSION: Our study shows that pulmonary rehabilitation is a feasible, safe and effective therapeutic option in COVID-19 patients independent of disease severity.

[COVID-19 and Headaches]. / COVID-19 und Kopfschmerzen.

COVID-19 and Headaches Abstract. Headaches are a common symptom of COVID-19 infections. Patients generally describe them as bilateral, predominantly frontal, squeezing and of moderate or severe intensity. Searching for "Red Flags" often allows distinction from primary headaches - usually fever, cough, and elevated inflammatory markers accompany COVID-19-associated headaches. Prospective studies did not confirm caveats against the use of ibuprofen as symptomatic treatment. While carrying facial masks often caused headaches, probably by compressing sensory nerves, many patients' migraine frequencies dropped during lockdown. Treatment of patients with primary headaches was complicated by quarantine and many centres offered online consultations.

Pathophysiology of COVID-19-associated coagulopathy and its impact on laboratory measures of coagulation

The article focuses on pathophysiology of COVID-19-associated coagulopathy and its impact on laboratory measures of coagulation. It mentions that cytokine storm is an unregulated and excessive release of pro-inflammatory cytokines, first locally in the infected lung and later, systemic throughout the body. It also mentions prothrombotic state in COVID- 19 patients causes an unprecedented range of thrombosis-related disorders in affected patients.