Coronavirus Infectious Disease 2019 Infection Research Articles

Indolent Lymphoma Care Delivery and Outcomes during the COVID-19 Pandemic in Ontario, Canada

Background At the outset of the coronavirus infectious disease 2019 (COVID-19) pandemic, hematological malignancy was recognized as a risk factor for severe COVID-19 disease, particularly patients with lymphoma, presenting a unique challenge for optimal management of indolent non-Hodgkin lymphoma (iNHL). To this end, professional societies including ASH favoured less immunosuppressive treatment regimens and omission of rituximab maintenance therapy. However, the implications of these recommendations on the care delivery and outcomes of patients with iNHL are unclear. Accordingly, we examined treatment selection, healthcare utilization, and COVID-19 outcomes of patients with iNHL receiving front line systemic treatment during pre-pandemic vs. pandemic period. Methods We performed a retrospective cohort study using administrative databases in Ontario, Canada, comparing outcomes in patients with iNHL who initiated first-line (1L) treatment with rituximab (R) monotherapy, or with bendamustine (B) or cyclophosphamide, vincristine, prednisone (CVP) from Jan 1, 2015 - Dec 31, 2018 (pre-pandemic cohort) and from Sept 1, 2019 - Aug 1, 2020 (pandemic cohort), with end of follow-up Mar, 31 2022. The primary outcome was comparison of treatment pattern before and during the COVID-19 pandemic which includes the following: 1L regimen received (R-CVP vs. B-R vs. R monotherapy), number of cycles received, dose delays, use of rituximab maintenance, and time-to-completion of full rituximab maintenance course (funded in Ontario every 3 months for 8 doses). Secondary outcomes were death, toxicities, healthcare utilization (emergency department [ED] visit, hospitalization, and ICU admission), and COVID-19 outcomes (SARS-CoV-2 PCR-confirmed infection, ED visit, hospitalization, and death). Adjusted odds ratios (aOR) and hazard ratios (aHR) with 95% confidence intervals (CI) from logistic regression and cause-specific proportional hazards models, respectively, were used to estimate associations between covariates (age, sex, comorbidity burden as measured by Aggregated Disease groups) and outcomes. Results We identified 4,143 patients (1,079 pandemic, 3,064 pre-pandemic), median age 69 (interquartile range 60-76) years, 44% female. In both pre- and pandemic periods, B-R was the most frequent prescribed regimen, with no difference in number of cycles given or in treatment delays (Table). During the pandemic, fewer patients received rituximab maintenance (69.6% vs 75.9%; aOR 0.72, 95% CI 0.60-0.88, p=0.0012). Older age was associated with lower odds of rituximab maintenance initiation (age 75+ vs. age < 60 aOR 0.44, 95% CI 0.35-0.56, p<0.0001). Moreover, patients who initiated maintenance during the pandemic period were less likely to complete the full maintenance course (48.7% vs 56.3%) (aHR 0.81, 95% confidence interval [CI] 0.71-0.92, p=0.0010) (Table) (Figure). Patients treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p<0.0001; hospitalization aHR 0.81, 95% CI 0.70-0.94, p=0.0067) and treatment-related complications (infection aHR 0.69, 95% CI 0.57-0.82, p<0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47-0.94, p=0.020), with no difference in death (aHR 0.79, 95% CI 0.58-1.08, p=0.14, Table). For COVID-19 outcomes, there were 131 SARS-CoV-2 infections from the beginning of the pandemic until December 31, 2021; with follow-up until March 31, 2022, there were 30 ED visits, 56 hospital admissions, and 23 ICU admissions, and 45 deaths related to COVID-19. Rituximab use (first dose to 1-year post-last dose) was associated with higher risk of COVID-19 infection (aHR 1.56, 95% CI 1.09-2.24, p=0.015) and COVID-19 complications (ED visit aHR 4.28, 95% CI 1.79-10.26, p=0.001; hospitalization/death 1.81, 95% CI 1.11-2.93, p=0.016). Primary vaccination series was associated with lower risk of infection and severe outcomes (infection aHR 0.52, 95% CI 0.28-0.97, p=0.04; hospitalization/death aHR 0.36, 95% CI 0.14-0.94, p=0.036; death aHR 0.26, 95% CI 0.07-0.89, p=0.033). Conclusion During the pandemic, B-R remained the preferred regimen for iNHL treatment, while rituximab maintenance use was less. Despite similar 1L regimen use, healthcare utilization and infectious complications were less in the pandemic cohort. Rituximab use was associated with nearly 2-fold risk of COVID-19 hospitalization/death.

The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses.

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of "common cold". In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and β-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

Differences in symptoms and utility of MEWS score in geriatric patients with COVID-19

Introduction: Rational resource management was key to avoiding overcrowding in Coronavirus Infectious Disease 2019 (COVID-19) dedicated wards. The study aimed to identify specific symptoms for aged patients with COVID-19 and assess the utility of the Modified Early Warning Score (MEWS) as a tool that may support decisions within an emergency department (ED). Material and methods: This was a retrospective analysis of medical records. ED patients with positive antigen tests for COVID-19 infection were identified. Patients’ history, length of stay (LOS) and vital signs were collected. MEWS score was calculated. Age groups were divided as follows: non-geriatric (NG) — aged under 60; geriatric groups (G): G1 — aged 60–74; G2 — aged 75–89; G3 — aged 90 and over. Results: There were 777 individuals (261 NG and 510 G patients). Symptoms related to pain as well as anosmia and ageusia occurred more often in NG patients. The longest LOS was in G2 — 182 [101–295] minutes. A significantly shorter LOS (51 [24–156] minutes) was recorded in NG (NG vs. G1 p < 0.0001; NG vs. G2 p < 0.0001; NG vs. G3 p = 0.0007). Admission rate was as follow: NG: 17.24%, G1: 50.97%, G2: 61.43%, G3: 54.17. Accuracy parameters for MEWS score (NG vs G, [%]) were as follow: sensitivity (93.18 vs. 91.04), specificity (13.04 vs. 11.79), positive predictive value (18.55 vs. 52.88), negative predictive value (90.00 vs. 54.76). Conclusions: Geriatric patients spent more time in ED and were admitted more often. Seniors were less likely to experience pain. MEWS is not a valuable tool for supporting decisions concerning the admission or discharge of geriatric patients with COVID-19.

COVID-19 and Tuberculosis: Two Knives in a Sheath

Abstract:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has caused a global human outbreak, making it a more serious threat to human health than any other infectious disease. Coronavirus infectious disease 2019 (COVID-19) has severely affected the lifestyles of people around the world and caused high mortality throughout the world. In both pandemic and seasonal influenza, co-infection of COVID-19 with other diseases has been linked to worse outcomes. The literature revealed that it is characteristically associated with comorbidities such as hypertension, blood pressure, obesity, cardiovascular diseases, and other microbial infections. Furthermore, microbial coinfections worsen respiratory viral infections and are a common cause of death in influenza pandemics. Deplorably, Tuberculosis (TB) is also a dreadful lung infection and attains cytokine equilibrium with host cells to maintain the latent stage. Studies showed that human coronaviruses (hCoV) activate latent TB to an active state due to unregulated cytokine production, called a cytokine storm. The present review concisely discusses the reason and status of co-infection of COVID-19 with TB based on previous case reports, cohorts, and scientific studies. COVID-19 patients are prone to be infected with TB and vice-versa in TB-prone areas. The therapeutic opportunities for overcoming the COVID-19 induced cytokine storm have also been emphasized by the present clinical trial candidates. In conclusion, we recommend categorizing the patients based on their medical history and cured or latent TB patients should be particularly closely monitored. They should be tested for Interferon Gamma Release Assay (IGRA) regularly on and after COVID-19 infection.

Investigation of the Clinical Laboratory Indexes in COVID-19 Patients with Ocular Symptoms in Iran: A Single-Center Experience

Objectives: Ocular symptoms are prevalent in coronavirus infectious disease 2019 (COVID-19) patients, which may be related to clinical/paraclinical conditions. This study investigated the association between laboratory indexes and ocular symptoms in COVID-19 patients. Methods: In this cross-sectional study, 108 polymerase chain reaction (PCR)-confirmed COVID-19 patients admitted to the Rouhani Hospital, Babol, Iran, were enrolled. Ocular symptoms were investigated using standard ophthalmologic examinations. Routine laboratory investigation was done according to the standard management in patients with COVID-19 infection. Results: The erythrocyte sedimentation rate (ESR) and the serum levels of the blood urea nitrogen (BUN) and creatinine (Cr) were significantly higher in COVID-19 patients with ocular discharge and exudate (P = 0.002, 0.045, 0.046, and 0.027, respectively), while the red blood cell (RBC) and albumin were lower in COVID-19 patients with ocular discharge and exudate (P = 0.029 and 0.027, respectively). The serum levels of creatine kinase (CPK) and iron (Fe) were significantly higher in non-photophobic COVID-19 patients than in photophobic patients (P =0.033 and 0.050, respectively). In contrast, the serum level of procalcitonin was lower than photophobic COVID-19 patients (P = 0.024). The serum level of phosphorus (P) was significantly higher in COVID-19 patients with itchy eyes compared to COVID-19 patients without itchy eyes (P = 0.026). Conclusions: The footprint of laboratory indexes was demonstrated in ocular symptoms of COVID-19 patients. The kidney biomarkers were correlated with ocular discharge and exudate, and electrolytes were associated with tear-related symptoms.

Acute ischemic events after COVID-19 infection in patients undergoing maintenance hemodialysis.

Patients undergoing maintenance hemodialysis have unique risk factors that render them prone to ischemia. To what extent coronavirus infectious disease 2019 (COVID-19) increases this risk is unknown. This retrospective cohort study included incident patients undergoing maintenance hemodialysis from one city in Turkey. A comparison was made between those who developed COVID-19 and those who did not for clinical variables. Independent predictors of acute ischemic complications in the total cohort were assessed using the logistic regression analysis. By the start of the pandemic in Turkey, 33 of 154 (21.4%) patients developed COVID-19. During the 15 months of median follow-up after the start of the pandemic, 16 (10.4%) patients developed acute ischemic complications. These included acute myocardial infarction (n=10), acute ischemic stroke (n=4), acute peripheral artery thrombosis (n=1), and pulmonary thromboembolism (n=1). Overall, acute ischemic events occurred more commonly in those who experienced COVID-19 (24.2% vs. 6.6%, p=0.007). Ischemia-free survival was significantly shorter in the COVID-19 group (p=0.001). In the eight patients with COVID-19, ischemic complications emerged at a median 185 (range 21-306) days after the diagnosis of COVID-19. While age, dialysis vintage, and experience of COVID-19 were found as factors significantly associated with the development of acute ischemic events in univariate analysis, the association between COVID-19 and acute ischemia remained significant in the multivariate regression model (odds ratio 3.99, 95% CI [1.3, 12.13], p=0.016). During the pandemic, 23 (14.9%) patients died. Overall survival was significantly shorter among those who developed acute ischemic event (p < 0.001). The hazard ratio of acute ischemic event for death was 6.76 (95% CI [2.92, 15.66], p < 0.001). A considerable number of patients undergoing maintenance hemodialysis developed acute ischemic complications weeks to months after the resolution of COVID-19. Hemodialysis patients appear to require specific interventions in order to prevent subsequent acute ischemic events after the resolution of COVID-19.

Health Issues and Immunological Assessment Related to Wuhan's COVID-19 Survivors: A Multicenter Follow-Up Study.

Background: Currently, a large number of hospitalized coronavirus infectious disease-2019 (COVID-19) patients have met the clinical discharge criteria and have been discharged. Little is known about the sequelae and herd immunity, two important factors influencing the life quality and safety of COVID-19 survivors.Methods: Discharged COVID-19 patients from four medical facilities in Wuhan, China, were followed in order to record and investigate possible post-COVID-19 sequelae and herd immunity. After hospital discharge, patients reported to Fangcang shelter hospitals for an initial 14-day period of mandatory clinical monitoring. After release from these shelter hospitals, patients returned home for self-quarantine. Real-time quantitative PCR (RT-qPCR) was used for severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) detection. Colloidal gold-based immunochromatographic strip assay (ICGSA) was used for anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody testing. The data for this study are derived from case reports, medical records, and self-reports.Results: A total of 3,677 COVID-19 survivors [median age = 59 years, interquartile range (IQR) = 47–68, range = 10–98; 55.5% female] who were released from four hospitals in Wuhan, China, between January 18 and March 29, 2020 were followed for a median of 144 days (IQR = 135–157). During follow-up, 976 (26.5%) patients had at least one post-COVID-19 sequela. The incidence of post-COVID-19 sequelae among elderly COVID-19 survivors (age ≥60 years) was slightly increased compared to that of young COVID-19 survivors (age <60 years; relative risk = 1.05, 95% CI = 1.02–1.10, p = 0.007). During follow-up, a dramatic reduction of anti-SARS-CoV-2 IgG (88.0%, 95% CI = 84.2–90.4) and IgM (93.2%, 95% CI = 88.5–96.4) antibodies was observed. Among these COVID-19 survivors, 1.2% (n = 45) retested positive for SARS-CoV-2 and 1.0% (n = 37) died during follow-up. Of those who died during follow-up, 70.3% were male and all were negative for both IgG and IgM, except for one person who was IgG-positive.Conclusions: Our study documents significant post-COVID-19 sequelae that impair functions of multiple organ systems in COVID-19 survivors, suggesting that the long-term effects of this disease will negatively impact survivors' quality of life, continue to strain health care systems, and result in extended periods of lost productivity. Furthermore, female gender and anti-SARS-CoV-2 immunity may play an essential role in the survival after COVID-19 infection.

Nationwide Seroprevalence of SARS-CoV-2 in Saudi Arabia

BackgroundEstimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients. MethodsA total of 11,703 serum samples were collected from different regions of the KSA including; 5395 samples from residual healthy blood donors (D); 5877 samples from non-COVID patients collected through residual sera at clinical biochemistry labs from non-COVID patients (P); and 400 samples from consented HCWs. To determine the seroprevalence of SARS-CoV-2, all serum samples, in addition to positive control sera from RT-PCR confirmed COVID-19 patients, were subjected to in-house ELISA with a sample pooling strategy, which was further validated by testing individual samples that make up some of the pools, with a statistical estimation method to report seroprevalence estimates. ResultsOverall (combining D and P groups) seroprevalence estimate was around 11% in Saudi Arabia; and was 5.1% (Riyadh), 1.5% (Jazan), 18.4% (Qassim), 20.8% (Hail), 14.7% (ER; Alahsa), and 18.8% in Makkah. Makkah samples were only D group and had a rate of 24.4% and 12.8% in the cities of Makkah and Jeddah, respectively. The seroprevalence in Saudi Arabia across the sampled areas would be 12 times the reported COVID-19 infection rate. Among HCWs, 7.5% (4.95–10.16 CI 95%) had reactive antibodies to SARS-CoV-2 without reporting any previously confirmed infection. This was higher in HCWs with hypertension. The study also presents the demographics and prevalence of co-morbidities in HCWs and subset of non-COVID-19 population. InterpretationOur study estimates the overall national serological prevalence of COVID-19 in Saudi Arabia to be 11%, with an apparent disparity between regions. This indicates the prevalence of asymptomatic or mild unreported COVID-19 cases.

Overview of an Emerging Coronavirus Infection, COVID-19: Current Status of Vaccine Development and Therapeutics

Coronavirus infectious disease 2019 (COVID-19) first reported in Wuhan, China, causes serious respiratory illnesses such as lung failure and pneumonia. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) the pathogenic agent of COVID-19 has been confirmed as a novel coronavirus. WHO announced COVID-19 a global pandemic and now the whole world is eagerly waiting for vaccines and therapeutic treatment to get rid of this unstoppable coronavirus. As COVID-19 infection, a global threat creates unwanted human casualties and serious economic loss. To stop the ongoing uncontrolled situation researchers are racing to develop prevention and treatment strategies. Vaccines of different countries are in clinical and preclinical trials and the repurposed-drugs are providing to find out a positive result against COVID-19. The report is an analysis of published information focusing on treatment options including vaccination, drug-therapy, cytokines, therapeutic antibodies. Most of the vaccine’s development strategies and drugs target the surface structural spike glycoprotein or S-protein, the major inducer of pathogenic responses. Here, it is reviewed the features of SARS-CoV-2 and the global current status of therapeutic, and vaccine development for the prevention and effective treatment of COVID-19.

Nationwide Seroprevalence of SARS-CoV-2 in Saudi Arabia

Background: Estimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of the COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients.Methods: A total of 11703 serum samples were collected from different regions of the KSA including; 5395 samples from residual healthy blood donors (D); 5877 samples from non-COVID patients collected through residual sera at clinical biochemistry labs from non-COVID patients (P); and 400 samples from consented HCWs. To determine the seroprevalence of SARS-CoV-2, all serum samples, in addition to positive control sera from RT-PCR confirmed COVID-19 patients, were subjected to in-house ELISA with a sample pooling strategy, which was further validated by testing individual samples that make up some of the pools, with a statistical estimation method to report seroprevalence estimates.Results: Overall (combining D and P groups) seroprevalence estimate was around 11% in Saudi Arabia; and was 5.1% (Riyadh), 1.5% (Jazan), 18.4% (Qassim), 20.8% (Hail), 14.7% (ER; Alahsa), and 18.8% in Makkah. Makkah samples were only D group and had a rate of 24.4% and 12.8% in the cities of Makkah and Jeddah, respectively. The seroprevalence in Saudi Arabia across the sampled areas would be 12 times the COVID-19 infection rate. Among HCWs, 7.5% (4.95-10.16 CI 95%) had reactive antibodies to SARS-CoV-2 without reporting any previously confirmed infection. This was higher in HCWs with hypertension. The study also presents the demographics and prevalence of co-morbidities in HCWs and subset of non-COVID-19 population.Conclusion: Our study estimates the overall national serological prevalence of COVID-19 in Saudi Arabia to be 11%, with an apparent disparity between regions.Funding Statement: This study was funded by KAIMRC, Grant: RC20/180; PI: Naif K. Alharbi.Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: The study was approved by the IRB in KAIMRC (Ministry of National Guard Health Affairs) for project number RC20-180. Residual samples from blood banks and clinical laboratories were obtained after an IRB approval. COVID-19 patients and HCWs signed informed consents to give blood samples.

COVID-19 pandemic in Yemen: A questionnaire based survey, what do we know?

Coronavirus infectious disease 2019 (COVID-19) is currently one of the most important public health crises affecting the global human population. It continues to spread widely, as the world still lacks specific treatments and a vaccine for the virus. The scenario of COVID-19 in Yemen seems obscure due to the lack of adequate data, therefore, we developed an electronic questionnaire and distributed it online among Yemeni people. The aim of this study was to understand the COVID-19 epidemiological situation in Yemen better since there is currently limited published data and limited availability of COVID-19 testing. A 34-question web-based survey was distributed on social media outlets targeting people in Yemen. Data aggregation, analysis, and visualization were performed using Tableau and Microsoft Excel. 2,341 individuals reported symptoms concerning for COVID-19 infection, with 25.4% reporting a chronic medical condition. Diabetes, hypertension, asthma, and immune deficiency were associated with increased severity of the disease, while obesity, cardiovascular disease, kidney disease, and liver disease were not. Only 37 individuals (1.6%) had a confirmatory COVID-19 PCR test. The presence of high fever, dyspnea, chest pain, and dysphagia were symptoms that tended to be correlated to worse clinical outcomes. This study provides some important information about the early overspread of COVID-19 within the Yemeni community in May, June, and July of 2020. It shows that online questionnaires may help in collecting data about pandemics in resource-limited countries where testing availability is limited.

Biomimetic Nanoparticles Potentiate the Anti-Inflammatory Properties of Dexamethasone and Reduce the Cytokine Storm Syndrome: An Additional Weapon against COVID-19?

Recent studies on coronavirus infectious disease 2019 (COVID-19) pathophysiology indicated the cytokine release syndrome induced by the virus as the main cause of mortality. Patients with severe COVID-19 infection present a systemic hyper inflammation that can lead to lung and multi-organ injuries. Among the most recent treatments, corticosteroids have been identified to be effective in mitigating these catastrophic effects. Our group has recently developed leukocyte-derived nanovesicles, termed leukosomes, able to target in vivo the inflamed vasculature associated with pathological conditions including cancer, cardiovascular diseases, and sepsis. Herein, to gain insights on the anti-inflammatory properties of leukosomes, we investigated their ability to reduce uncontrolled inflammation in a lethal model of lipopolysaccharide (LPS)-induced endotoxemia, recapitulating the cytokine storm syndrome observed in COVID-19 infection after encapsulating dexamethasone. Treated animals showed a significant survival advantage and an improved immune response resolution, as demonstrated by a cytokine array analysis of pro- and anti-inflammatory cytokines, chemokines, and other immune-relevant markers. Our results showed that leukosomes enhance the therapeutic activity of dexamethasone and better control the inflammatory response compared to the free drug. Such an approach could be useful for the development of personalized therapies in the treatment of hyperinflammation related to infectious diseases, including the ones caused by COVID-19.

COVID-19 Associated Ischemic Stroke and Hemorrhagic Stroke: Incidence, Potential Pathological Mechanism, and Management.

The outbreak of the novel coronavirus infectious disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has rapidly spread around the world. Increasing evidence has suggested that patients with COVID-19 may present neurological symptoms, and cerebrovascular diseases are one of the most frequent comorbidities. The markedly elevated D-dimer levels in patients with acute ischemic stroke suggests that SARS-CoV-2 infection may induce an inflammatory response and trigger a hypercoagulation state, thus leading to acute ischemic stroke. Cardioembolism and atherosclerosis in patients with COVID-19 infection may also increase the risk of ischemic stroke. The reduction of the angiotensin-converting enzyme II (ACE2) caused by SARS-CoV-2 binding to the ACE2 receptor can lead to abnormally elevated blood pressure and increase the risk of hemorrhagic stroke. Additionally, the cytokine storm induced by the immune response against the viral infection increases the risk of acute stroke. The management for COVID-19 patients with stroke is not only based on the traditional guidelines, but also based on the experience and new instructions from healthcare workers worldwide who are combatting COVID-19.

Pathophysiology and Pathology of Acute Kidney Injury in Patients With COVID-19.

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries

BackgroundIncreasing evidence suggests pernio-like lesions are cutaneous manifestations of coronavirus infectious disease 2019 (COVID-19).ObjectiveTo describe clinical and pathologic findings of pernio-like lesions in patients with confirmed or suspected COVID-19.MethodsAn international dermatology registry was circulated to health care providers worldwide through the American Academy of Dermatology, International League of Dermatologic Societies, and other organizations.ResultsWe documented 505 patients with dermatologic manifestations associated with COVID-19, including 318 (63%) with pernio-like lesions. Patients with pernio-like lesions were generally young and healthy, with relatively mild COVID-19. Of 318 patients with confirmed or suspected COVID-19 by providers, 23 (7%) were laboratory-confirmed COVID-19 positive, and 20 others (6%) were close contacts of patients with confirmed COVID-19. Given current testing criteria, many patients lacked COVID-19 testing access. For 55% of patients, pernio-like lesions were their only symptom. In patients with other COVID-19 symptoms, pernio-like lesions typically appeared after other symptoms. Pernio-like lesions lasted a median of 14 days (interquartile range, 10-21 days).LimitationsA case series cannot estimate population-level incidence or prevalence. In addition, there may be confirmation bias in reporting. We cannot exclude an epiphenomenon.ConclusionsPernio-like skin changes of the feet and hands, without another explanation, may suggest COVID-19 infection and should prompt confirmatory testing.

Radiological findings for diagnosis of SARS-CoV-2 pneumonia (COVID-19)

On 31st December 2019, China reported that several cases of pneumonia of unknown origin had occurred in Wuhan (Hubei Province), the cause of which was identified on 7th January 2020: a new coronavirus initially named 2019 novel coronavirus (2019-nCoV). On 11th February, the World Health Organization (WHO) renamed the new virus SARS-CoV-2 due to the similarities between the cause of the severe acute respiratory syndrome that broke out in 2003 and COVID-19 (Coronavirus Infectious Disease 2019).1 On 30th January, WHO declared the outbreak a Public Health Emergency of International Interest, and a pandemic on 11th March. As of 21st March 2020, 311,314 cases have been reported in 188 affected countries, with 13,079 deaths as a result of the infection and 95,800 people recovered (https://www.worldometers.info/coronavirus/). The statistics probably reflect a bias toward the most serious cases, which have more contact with the health system. However, many cases may be undiagnosed, as they are asymptomatic patients who do not go to a health center or mild symptomatology cases that are not confirmed due to the limited availability of diagnostic tests in many countries, such as Spain. Therefore, these statistics are likely to underestimate mild and asymptomatic cases, with the pandemic having a higher prevalence.2 COVID-19 infection can develop as a mild, moderate, or severe illness, including severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and septic shock. The incubation period ranges from about 5 days (interval: 4–7 days) to a maximum of 12–13 days. Mild cases may develop flu-like symptoms: high fever, myalgia, fatigue, and respiratory symptoms, especially dry cough, with possible progression to pneumonia. The onset is usually less abrupt than in the flu, and upper respiratory symptoms seem minor or absent.2, 3 The main source of infection is other patients already infected with SARS-CoV-2. This is transmitted through respiratory droplets (aerosols > 5 μm) over short distances (1.5–2 m) when patients cough, speak or sneeze, and through contaminated hands when in close contact with the mouth, nose, or bulbar conjunctiva. Prolonged contact represents the highest risk, with casual contacts being less likely to cause contagion. There can be infections from asymptomatic patients and even from people in the incubation period of the disease.2, 4 Transmission through infected surfaces is likely, with SARS-CoV-2 recently reported to remain on plastic and stainless steel up to 72 h.5 The diagnosis of COVID-19 disease is made through reverse transcription polymerase chain reaction [RT-PCR]) with the detection of nucleic acids of SARS-CoV-2 or by the virus's genetic sequencing. Pharyngeal or nasopharyngeal smear samples, sputum, stools, or blood may be used. The virus can also be isolated in airway epithelial cell cultures, but this is done exclusively in specialized laboratories.6 Therefore, RT-PCR screening is regarded as the gold standard laboratory test for the diagnosis of COVID-19. False negatives have been documented in some cases, likely due to inappropriate viral sample material or technical problems during nucleic acid extraction.7, 8, 9 The incidence of COVID-19 has been observed to be higher in men than in women, for which the influence of the X chromosome and sex hormones on innate and adaptive immunity has been suggested as a possible explanation.10, 11 The respiratory system is the first to be affected by COVID-19, so in suspicious cases it is common to request a chest X-ray (CXR) as the first imaging test. However, its diagnostic performance in the initial stages of the disease is limited, since it has been reported that pathological findings identifiable on chest computed tomography (CCT) may not be detected on X-rays.7, 12, 13 This fact, together with the initial circumstances of the epidemic, when the accumulation of suspected cases exceeded the availability of RT-PCR tests, led to certain working groups adopting CCT as a diagnostic test in the absence of RT-PCR, leading to an unprecedented number of CCT studies to try to characterize a novel infectious disease. The CCT obtained very good results in these studies, observing that the pathological findings of the CCT can occur even before the symptoms7, 12, 13 and be diagnostic in patients with initial RT-PCR false-negative results.7, 8, 14 Therefore, it was concluded that CCT is a very valuable tool to diagnose COVID-19 infection, both in the initial assessment of lung involvement and for its follow-up.7, 15, 16 This article aims to identify the characteristics of this rapidly progressive viral pneumonia on imaging tests, both on CXR and CCT. The characteristic imaging findings of the different stages of the disease, the evolution of the findings associated with the progression of the disease or with clinical improvement, and the variation in the prevalence of the different patterns according to the age of the patients are also explained.