REVIEW ARTICLE
Year : 2020 | Volume
: 4 | Issue : 3 | Page : 99--105
COVID-19: The latest news and views
Khalid Farooqui1, Samman Rose1, Abdelnasser Y AwadElzouki2,
1 Department of Medicine, Hamad Medical Corporation, Qatar
2 Department of Medicine, Hamad Medical Corporation; Weill Cornell Medicine, Doha, Qatar
Correspondence Address:
Dr. Khalid Farooqui
Department of Medicine, Al Khor Hospital , Hamad Medical Corporation, Doha
Qatar
Abstract
COVID 19 pandemic in 6-8 months has left many countries in a devastating state , it has caused mortality and disabilities with different mechanism in the body which have been continuously evolving since the origin of the SARS COV2 virus causing great social, psychological and financial burden on the countries around the world. As we all know it's a viral infection with been different theories suggesting different action of SARS COV2, which have been evolved in last few months and still its ongoing to understand the exact nature of its virulence with its involvement of different mechanism of actions in different population which not only makes difficult in clinical prediction , prognosis but also its utmost challenging in the management and treatment of COVID 19 infection. In our review article we mainly emphasize over the recent updates involved in different action of SARS COV2 infection on different organs of human body, its virulence variation in selected populations, clinical predictors. We also briefly discuss about the latest modality of management for SARS COV2 infection along with treatment regimens and updates on vaccination.
How to cite this article:
Farooqui K, Rose S, AwadElzouki AY. COVID-19: The latest news and views.Libyan J Med Sci 2020;4:99-105
|
How to cite this URL:
Farooqui K, Rose S, AwadElzouki AY. COVID-19: The latest news and views. Libyan J Med Sci [serial online] 2020 [cited 2023 Mar 30 ];4:99-105
Available from: https://www.ljmsonline.com/text.asp?2020/4/3/99/295621 |
Full Text
Virology News and Views
SARS-CoV-2 seems to have similar mechanisms for receptor recognition to those used by prior virulent coronaviruses such as SARS-CoV1. The coronavirus spike protein facilitates entry of the virus into target cells engaging ACE2 (angiotensin-converting enzyme 2) as an entry receptor. Hoffmann et al., recently proposed another important mechanism in the cell entry requires catalyzing of the spike protein by the cellular serine protease TMPRSS2 and some other proteases.[1] Both receptor expressions at cellular level are essential for the completion of this entry process of SARS COV2 virus. In addition, the efficiency with which the virus binds to ACE2 is a key determinant of transmissibility, as shown in previous studies.[2] There are mainly three mechanism involved in multiorgan injury secondary to SARS COV2 infection:
Direct viral toxicity
SARS-CoV-2 is transmitted mainly through direct or indirect respiratory-tract exposure. Histopathological studies have reported organotropism of SARSCoV-2 into multiple organs including respiratory tract, renal, myocardium, brain, and gastrointestinal tissues.[3],[4],[5],[6],[7]
Puelles et al., were first quantified the SARS-CoV-2 viral load in autopsy tissue samples obtained from 22 patients who had died from Covid-19 for in situ hybridization and immunofluorescence of various organs, showing SARS-CoV-2 RNA detection.[3] These results indicate that SARS-CoV-2 has an organotropism beyond the respiratory tract, involving multiple organs; and therefore, the course of COVID-19 disease may aggravate preexisting conditions. A study by Xiao et al. showed evidence and clinical significance of gastrointestinal manifestation of SARS COV2 infection with swabs and tissues from 73 hospitalized patients infected with SARSCoV-2.[7] Histologic and immunofluorescent staining of the biopsy tissue sample was performed and the authors observed that ACE2 staining is rarely seen and less expressed in esophageal mucosa. The authors concluded that despite the nasopharyngeal reverse transcriptase-polymerase chain reaction (RT-PCR) swab test being negative, interestingly in more than 20% of patients with SARS-CoV-2, the viral RNA remained positive in feces, indicating that the viral gastrointestinal infection and potential fecal-oral transmission can last even after viral clearance in the respiratory tract. It was strongly recommended that rRT-PCR testing for SARS-CoV-2 from feces should be performed routinely in patients with SARS-CoV-2 and those transmission-based precautions should be performed.
Endothelial cell damage and thrombo-inflammation
An endothelial injury mediated by SARS-CoV-2 infection using an ACE2-mediated entry and subsequent inflammation and the generation of a prothrombotic milieu are the possible mechanisms.[8],[9] Similarly, infection-mediated endothelial injury and endothelialitis has been reported in multiple vascular beds of the lungs, kidney, heart, small intestine, and liver in patients, which can trigger excessive thrombin production, inhibit fibrinolysis, and activate complement pathways, initiating thrombo-inflammation and ultimately leading to microthrombi deposition and microvascular dysfunction.[9],[10],[11]
Cytokine released from platelet–neutrophil cross-communication and activation of macrophages can lead to the formation of neutrophil extracellular traps, and fibrin and/or microthrombus formation.[12] Direct coronavirus-mediated effects may also lead to an imbalance of pro- and anti-coagulant pathways leading to thrombo-embolism.[13],[14]
Varga et al. demonstrated direct evidence of the presence of viral proteins in the endothelial cell.[9] This can probably lead to the accumulation of inflammatory cells, with evidence of endothelial and inflammatory cell death. The study suggests that SARS-CoV-2 infection facilitates the induction of endotheliitis in multiorgans as a direct consequence of viral involvement. Similarly, autopsy findings of COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19.
Dysregulation of the immune response
Dysfunctional immune response and cytokine-release syndrome, due to over activation of T-cell lymphodepletion, were found in severe COVID-19 infection. Elevation of serum inflammatory markers such as C-reactive protein, ferritin, erythrocyte sedimentation rate, D-dimer, fibrinogen, and lactate dehydrogenase, higher interleukin levels is predictive of subsequent critical illness and mortality in patients with COVID-19.[15],[16] Petrilli et al., demonstrated in a prospective cohort study the clinical outcomes in terms of admission to hospital, critical illness requiring intensive care, mechanical ventilation and discharge to hospice care or death.[16] The results showed inflammatory markers (C-reactive protein, troponins, and D-dimer levels) were more strongly associated with critical illness and mortality than age and comorbid conditions.
Epidemiology of Covid-19 News and Views
Prevalence
As of August 10, 2020, it has been estimated to reach 20 million registered cases of COVID-19 and 750,000 deaths.[17]
Incubation period
Current estimates suggest a median incubation period from 5 to 6 days for COVID-19, with a range from 2 to 14 days.[18]
Transmission of infection
The spread of the disease has been mainly through droplet infection, surface contamination, and fecal-oral route.
Intrauterine transmission
although apparently unlikely, cannot be ruled-out.[19],[20] Positive RT-PCR results from placental samples have been reported, without infection in the neonates.[21],[22] Yan et al., evaluated in a retrospective study of 116 pregnant patients, the clinical characteristics and outcomes in pregnancy and the vertical transmission.[20] The amniotic fluid, cord blood, and neonatal pharyngeal swab samples were taken. The study concluded that SARS COV2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There was also no evidence of vertical transmission. However, thr three neonates born to women with confirmed COVID-19 who tested positive for immunoglobulin G and immunoglobulin M antibodies despite having a negative viral nucleic acid result.
Breast milk transmission
Only one study has reported positive RT-PCR results in breast milk from a mother with mild COVID-19,[23] however, the data are limited.
Air borne transmission
klompas et al. published a view point article in JAMA network which concluded that it is very difficult and impossible to conclude that aerosol-based transmission never occurs.[24] However, the balance of currently available evidence suggests that long-range aerosol-based transmission is not the dominant mode of SARS-CoV-2 transmission and it is perfectly understandable that many prefer to err on the side of caution, particularly in health-care settings when caring for patients with suspected or confirmed COVID-19. Most of the epidemiologic data are more supportive of droplet transmission being the predominant mechanism of the disease spread.
Transmission in domestic cats
The transmission of cats was studied by inoculating SARS COV-2 virus into previously uninfected cats and was found out to be infectious in 1–5 days of time confirmed by nasal swab RT-PCR, and also they continued to shed virus for further 4–5 days, however, no virus was detected in any of the rectal swabs tested.[25] There are reports of transmission of SARS-CoV-2 from humans to domestic cats as well as to tigers and lions at the Bronx Zoo, coupled with the present data showing the ease of transmission between domestic cats, it is very important that public health need to recognize and further investigate the potential chain of human–cat–human transmission. Cats may be considered as silent carriers as they may not show appreciable symptoms. Therefore, breaking transmission chains, a better understanding of the role cats may play in the transmission of SARSCoV-2 to humans is needed.
Clinical Manifestations of Covid-19 News and Views
COVID-19 infection widely varies from most common symptoms such as fatigue, dyspnea, arthralgia, chest pain, cough, anosmia, rhinitis, red eyes, dysgeusia, headache, repulsion to food, sore throat, myalgia, diarrhea to rare symptoms such as sputum production, sicca syndrome, and vertigo.[26] [Table 1] summarizes the extra-pulmonary manifestations of COVID-19.[27],[28] It is noteworthy that majority of these manifestations are based on case series or case reports.{Table 1}
Menni et al. created a mobile application for real-time tracking of self-reported symptoms to predict potential COVID-19.[29] The mobile device app allows users to report repeatedly on symptoms and data from more than 2.6 million people link loss of smell and taste to COVID-19 were collected. There were about 7000 confirmed RT-PCR-positive patients for COVID 19 and about 65% of the confirmed cases strongly reported symptoms of loss of taste and smell; thus, this study provides a strong associated between COVID 19 infection and symptoms of loss of taste and anosmia.
Diagnosis of Covid-19 News and Views
Still the present gold standard test in diagnosing COVID-19 infection is nasopharyngeal reverse transcriptase-polymerase chain reaction (RT-PCR) swab.[30],[31],[32] In a very recent study, Kucirka et al. analyzed pooled data from a mix of inpatients and outpatients with COVID-19 infection (n = 1330 patients) published in 7 studies providing information on RT-PCR performance by time since symptom onset of COVID-19 exposure.[33] They estimated the false-negative rate by day since start of the COVID-19 infection using a Bayesian hierarchical model. They found the probability of false-negative result in an infected person decreases from 100% on day 1% to 67% on day 4, and the median false-negative rate on the day of symptom onset was 38%. This decreased to 20% on day 8 (3 days after symptom onset) then began to increase again, from 21% on day 9 to 66% on day 21. The authors concluded that “care must be taken in interpreting RT-PCR tests for COVID-19 infection - particularly early in the course of infection - when using these results as a basis for removing precautions intended to prevent onward transmission.”[33] If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone, and the clinical and epidemiologic situation should be carefully considered.
Diagnostic accuracy of serological tests for COVID-19
Serology plays a role in diagnosing the later stages of COVID-19 infection, carrying a high rate of false negative if tested in early part of the disease. It used to determine the immune status of the person. Also provide data for seroprevalence studies which helps in effectively combating the 2nd wave of the COVID-19 infection. A systematic review and meta-analysis of about 40 studies,[34] assessed the primary outcome was to measure overall sensitivity and specificity for different serological tests and its interpretation. The sensitivity was 84.3% for enzyme-linked immunosorbent assays (ELISA) measuring IgG, IgM antibodies; 66% was for lateral flow immunoassays (LFIAs); 97.8% for chemiluminescent immunoassays. The pooled specificity was >96% for all the three serological tests. The sensitivity of LFIAs was lower in commercial kits in comparison with noncommercial kits, and importantly, the sensitivity was higher at 3 weeks after symptoms than that at 1st week. The authors suggested the urgent need for high quality studies to evaluate diagnostic accuracy of serological tests for COVID-19.
Treatment of Covid-19 News and Views
Metformin and COVID-19
Patients with diabetes and COVID-19 infection are at increased risk of significant adverse effects including increase risk of death. Metformin is an effective and cheaper drug that lowers blood sugar in patients with diabetes. A study by Carolyn et al.,[35] currently under publication process from University of Minnesota, studied the effect of metformin on patients with diabetes and COVID19 infections. The data include a total of 6256 persons with average age of 75 years. The team observed that metformin was associated with decreased mortality in women with obesity but had no significant reduction in mortality among men. A study by Luo et al.[36] from China, studied the clinical outcomes in patients with COVID-19 infection and concomitant diabetes. The patients were divided into two groups, those who were on metformin and other group patients on placebo. Although the duration of hospital stay did not differ between the two groups (21 days for metformin vs. 19.5 days for no metformin, P = 0.74). However, metformin group had significantly lower in-hospital mortality versus the other groups (2.9% vs. 12.3%, P = 0.01). The study suggests that metformin may offer benefits in patients with COVID-19 and further study is needed.
Statin and COVID-19
Zhang et al. published data collected from 13,981 patients who were admitted with COVID-19 disease to 21 hospitals from Hubei Province, China. The data were divided into (statin group) of 1,219 and the remaining (nonstatin group) of 12,762 patients.[37] The incidence rate of death during a 28-day follow-up in the statin group was 5.5% versus 6.8% in nonstatin group This is despite the fact that patients with statin-group were older (66 vs. 57 years of age, P < 0.001), had higher prevalence of chronic medical conditions, including hypertension, diabetes mellitus, coronary heart disease, cerebrovascular diseases, and chronic kidney diseases than those without statin treatment. Although the results were promising in see the real impact, it would need further larger prospective studies.
Antihypertensive medication and COVID-19
Recently, there has been conflicting recommendations about the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) for the treatment of hypertension and in patient with treated for COVID-19 infection. A study by Zhang et al.,[38] from 1,128 adult patients with hypertension and diagnosed with COVID-19 admitted to 21 hospitals from Hubei Province, China. The data included 188 patients taking ACEI/ARB and the remaining 940 non-ACEI/ARB group. The 28-day all-cause mortality was significantly lower in ACEI/ARB group versus non-ACEI/ARB group. Although the study is on relatively small number of patients, but it does suggest that it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.
Hydroxychloroquine and COVID-19, still any role?
Since the beginning of the COVID-19 pandemic, hydroxychloroquine has been recommended for the treatment and in some cases as preventive management leading to controversial news and clinical outcomes. A review study by Esposito et al.[39] summarized the trials which included the patients enrolled ranging from few hundred up to several thousands, various dosages and in addition to other combination drugs. The outcomes included viral clearance, fever/symptoms resolution, and other morbidity and mortality benefits. All these reported studies did not show clear benefits in terms of mortality or intubation. Still there are some ongoing trials. In summary, it seems that antimalarial medications may act synergistically with macrolides (e.g., azithromycin) for enhanced antiviral effect but the existing evidence is limited and studies had several limitations including lack of randomization and potential selection bias.
Tocilizumab and Covid-19
Tocilizumab is a recombinant monoclonal antibody of the IgG1 class that inhibits Interleukin-6, which is recommended for the treatment of severe rheumatoid arthritis, systemic juvenile idiopathic arthritis and other life-threatening conditions caused by cytokine release. The drug has been administered to patient with hospitalized severe COVID-19 in Qatar, China, and Italy. There have been various small case reports, small cohort clinical studies with conflicting results reported. Alattar et al. showed the clinical outcomes in 25 patients who received tocilizumab for very ill patients related to COVID-19 cytokine storm.[40] The patients showed a significant improvement in inflammatory markers, radiological improvement, and reduced ventilatory support requirements. There are ongoing FDA approved clinical trial (registration number NCT04320615), Italian trial called TOCIVID-19 and two trials in China with large number of patients.
Convalescent plasma transfusion and COVID-19
The usefulness and potential therapeutic benefits of a CCP transfusion of cured person from infectious diseases has been established in various viral infections, including those due to SARSCoV, Spanish influenza A (H1N1), avian influenza A (H5N1), and 2009 pandemic influenza A (H1N1). There has been several case reports, which suggested excellent outcomes in patients treated with plasma transfusion for COVID-19 patients. A recent study by Xia et al. published on August 6, data on 1568 patients with severe or critical COVID-19 from Wuhan Huoshenshan Hospital, China.[41] They included 1430 patients who received standard treatment only and 138 patients who also received ABO-compatible CCP transfusion. The results suggest that CCP transfusion could improve the symptoms and mortality in patients with severe or critical cases of COVID-19. Although this reported result has limitations for general recommendations, this may help in adopting larger trials for the use of CCP transfusion in the management of severely ill COVID-19 patients.
The use of steroids in COVID-19
The use of steroids in critical ill patient has been establish in some patients but its use in COVID-19 related critical illness were not fully established until the recent University of Oxford funded RECOVERY trial.[42] In this trial, 2,104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29% vs. 40.7%, P = 0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25%, P = 0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, P = 0.14). Similarly, there have been other small studies and case reports with varying degree of steroids effect in critically ill patients with COVID-19. The use of steroids should be considered in individual local guidance of COVID-19 treatment.
Therapeutic plasma exchange and COVID-19
The use of therapeutic plasma exchange (TPE) was initially described by Keith et al.[43] and then by Tian et al.,[44] in 37 patients with COVID19 infection. Tabibi et al.[45] assess in their review article about the use of TPE use in critically ill patients with COVID19 disease. TPE has been successfully used in the treatment of acute respiratory distress syndrome secondary to H1N1 influenza, Myasthenia gravis patient, Kawasaki disease-induced vasculitis coagulopathies, and adults with DIC and multiorgan failure. The authors conclude that TPE can be considered in certain cases as also approved by the FDA for new emergency use in critically ill COVID-19 patients but needs more clinical evidence.
Covid-19 Vaccines News and Views
Immunogenicity and safety of a recombinant adenovirus type-5-vectored (Ad5-vectored) COVID-19 vaccine in healthy adults
This is first phase II randomized double blind placebo controlled trial for the evaluation of immunogenicity and safety of Ad5-vectored COVID-19 vaccine which was carried out among healthy adults in Wuhan China.[46] Participants were screened for HIV and SARS COV-2 infection and about 508 eligible candidates randomly assigned were injected intramuscularly dose of vaccine either 1 × 1011 viral particles per ml or 5 × 1010 viral particles per ml. Both evaluated doses were compared with placebo and it showed the AD-5-vectored COVID-19 vaccine induced significant neutralizing antibody response to SARS-COV-2 by ELISA method, with no serious adverse reactions. The novel vaccine is found to be safe, better tolerated at different doses and induces significant immune response. In most of the evaluated patients and phase-III trail is planned for the evaluation of efficacy.
An mRNA vaccine against SARS-CoV-2
This is Phase I dose escalation open-labeled trial which included 45 healthy adults between age of 18–55 years screened negative for SARS-COV-2 infection.[47] The vaccine was evaluated against SARS-COV-2 at three different dose levels, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants and it was observed that the antibody responses were higher with higher dose which was measured by ELISA technique. An immune response was registered in all participants with binding and neutralizing antibody titers similar to those found in convalescent serum specimens, and also to note that no trial limiting safety concerns were identified.
Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2
In this phase I and II, single-blind, randomized controlled trial in five different trial sites in the UK.[48] The chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein was compared with a meningococcal conjugate vaccine (MenACWY) as control, to assess the immunogenicity and safety of potential COVID-19 vaccine. The trial included healthy adults between the age of 18–55 years, were screened negative for RT-PCR nasopharyngeal swab test and randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. The safety of was assessed over 28 days after vaccination. The humoral response at baseline and after vaccination was assessed by total IgG antibody by ELISA technique and cellular response was done by ex vivo interferon-γ ELISA. The results showed neutralizing antibody responses in 91% of 35 patients receiving single dose of vaccine and then 100% response after a second dose of ChAdOx1 nCoV-19 vaccine. The novel vaccine is found to be safe in terms of immunogenicity and efficacy, which will be further evaluated in the ongoing phase III trial.
Other News and Views
Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes
Cariou et al.,[49] published a multicenter observational study in people with diabetes hospitalized for COVID-19 in 53 French centers.[49] The primary outcome was combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. The results showed out of the 1,317 participants, 29% required tracheal intubation (primary outcome), the microvascular and macrovascular complications were seen in 46.8% and 40.8%, respectively, with a mortality of 10.6%, and 18% were discharged on day 7. In people with diabetes hospitalized for COVID-19 infection, the study showed a long-term glucose control might have little impact on early COVID-19 prognosis but BMI was positively and independently associated with the risk of tracheal intubation and death within 7 days of infection.
What have lockdowns, social distancing, masks, and other measures achieved?
A multinational team of social scientists published modeled data collected on the effects of large-scale anti-contagion policies in six different countries in the world which includes China, South Korea, Iran, Italy, France, and the USA.[50] It was observed with modeled data anti-contagion measures such as lockdown, social distancing, and wearing masks has shown that an estimated 530 million COVID-19 cases possibly were prevented or delayed globally, thus preventing 2.65 million deaths if 0.5% COVID-19-related mortality is considered.
COVID-19 and its neuropsychiatric complications
Varatharaj et al.[51] examined case reports on 153 patients from registry of British neurological and psychiatric professional organizations. The clinical data were available for 125 hospitalized patients. The retrospectively observed that the most common neurological condition was a cerebrovascular event in 77 patients (62%), second-most common condition was followed by altered mental status in 39 patients (31%) which was found to be different pathology 9 patients had an encephalopathy, and 7 had encephalitis. The other 23 patients (59%) had psychiatric disorders including psychosis, a neurocognitive syndrome, and affective disorders; 2 patients experienced exacerbations of preexisting mental illness. Authors concluded that altered mental status was the second-most common manifestation and occurred more frequently in younger patients after cerebrovascular events.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
| 1 | Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80. |
| 2 | Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 2005;309:1864-8. |
| 3 | Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020;383:590-2. |
| 4 | Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020;323: 1843-1844. |
| 5 | Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020;98:219-27. |
| 6 | Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 2020;22:911-5. |
| 7 | Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020;158:1831-3000. |
| 8 | Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020;383:120-8. |
| 9 | Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8. |
| 10 | Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013;13:34-45. |
| 11 | Bikdeli B, Madhavan MV, Gupta A, Jimenez D, Burton JR, Nigoghossian CD, et al. Pharmacological agents targeting Thrombo-inflammation in COVID-19: Review and implications for future research. Thromb Haemost 2020;120:1004-24. |
| 12 | Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al., Neutrophil extracellular traps in COVID-19. JCI Insight 2020;5:e138999. |
| 13 | Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol 2020;127:104362. |
| 14 | Deshpande C. Thromboembolic Findings in COVID-19 Autopsies: Pulmonary Thrombosis or Embolism? Ann Intern Med. 2020;173:394-395. doi: 10.7326/M20-3255. Epub 2020 May 15. PMID:32422061; PMCID: PMC7249508. |
| 15 | Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46:846-48. |
| 16 | Petrilli CM, Jones SA, Yang J, Rajagopalan H, O'Donnell L, Chernyak Y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: Prospective cohort study. BMJ 2020;369:m1966. |
| 17 | Available from: https://www.who.int/docs/default-source/coronaviruse/covid-19-virtual-press-conference---10-august-at-12-pm-cest.pdf?sfvrsn=46fd5bbd_0. [Last accessed 2020 Aug 23]. |
| 18 | Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020. Euro Surveill. 2020;25:2000062. doi:10.2807/1560-7917. |
| 19 | Della Gatta AN, Rizzo R, Pilu G, Simonazzi G. Coronavirus disease 2019 during pregnancy: A systematic review of reported cases. Am J Obstet Gynecol 2020;223:36-41. |
| 20 | Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirus disease 2019 in pregnant women: A report based on 116 cases. Am J Obstet Gynecol 2020;223:111.e1-.11E+16. |
| 21 | Schwartz DA. An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: Maternal coronavirus infections and pregnancy outcomes. Arch Pathol Lab Med 2020;144:799–805. |
| 22 | Penfield CA, Brubaker SG, Limaye MA, Lighter J, Ratner AJ, Thomas KM, et al. Detection of severe acute respiratory syndrome coronavirus 2 in placental and fetal membrane samples. Am J Obstet Gynecol MFM.2020;2:100133. doi: 10.1016/j.ajogmf.2020.100133. Epub 2020 May 8. |
| 23 | Groß R, Conzelmann C, Müller JA, Stenger S, Steinhart K, Kirchhoff F, et al. Detection of SARS-CoV-2 in human breastmilk. Lancet 2020;395:1757-8. |
| 24 | Klompas M, Baker MA, Rhee C. Airborne transmission of SARS-CoV-2: Theoretical considerations and available evidence. JAMA 2020;324:441-2. |
| 25 | Halfmann PJ, Hatta M, Chiba S, Maemura T, Fan S, Takeda M, et al. Transmission of SARS-CoV-2 in domestic cats. N Engl J Med 2020;383:592-4. |
| 26 | Carfì A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324:603-5. |
| 27 | Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017-32. |
| 28 | Somasundaram NP, Ranathunga I, Ratnasamy V, Sachindra P, Wijewickrama A, Dissanayake HA, et al. The impact of SARS-Cov-2 virus infection on the endocrine system. J Endocr Soc 2020;4:bvaa082. |
| 29 | Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, et al. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med 2020;26:1037-40. |
| 30 | Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020;71:762-8. |
| 31 | Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China Intensive Care Med 2020;46:846-8. |
| 32 | Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62. |
| 33 | Kucirka LM, Lauer SA, Laeyendecker O, Boon D. Variation in false-negative rate of reversetranscriptase polymerase chain reaction-based SARS-CpV-2 tests by time since exposure. Ann Intern Med 2020;173:262-7. |
| 34 | Lisboa Bastos M, Tavaziva G, Abidi SK, Campbell JR, Haraoui LP, Johnston JC, et al. Diagnostic accuracy of serological tests for covid-19: Systematic review and meta-analysis. BMJ 2020;370:m2516. |
| 35 | Bramante CT, Ingraham NE, Murray TA, Marmor S, Hovertsen S, Gronski J, et al. Observational study of metformin and risk of mortality in patients hospitalized with COVID-19. MedRxiv. 2020;2020.06.19.20135095. doi:10.1101/2020.06.19.20135095. |
| 36 | Luo P, Qiu L, Liu Y, Liu XL, Zheng JL, Xue HY, et al. Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis. Am J Trop Med Hyg 2020;103:69-72. |
| 37 | Zhang XJ, Qin JJ, Cheng X, Shen L, Zhao YC, Yuan Y, et al. In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab 2020;32:176-870. |
| 38 | Zhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie J, et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res 2020;126:1671-81. |
| 39 | Esposito S, Noviello S, Pagliano P. Update on treatment of COVID-19: Ongoing studies between promising and disappointing results. Infez Med 2020;28:198-211. |
| 40 | Alattar R, Ibrahim TBH, Shaar SH, Abdalla S, Shukri K, Daghfal JN, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol. 2020;10.1002/jmv.25964. doi: 10.1002/jmv.25964. Online ahead of print. |
| 41 | Xia X, Li K, Wu L, Wang Z, Zhu M, Huang B, et al. Improved clinical symptoms and mortality among patients with severe or critical COVID-19 after convalescent plasma transfusion. Blood 2020;136:755-9. |
| 42 | Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. RECOVERY collaborative group, dexamethasone in hospitalized patients with Covid-19 – preliminary report. N Engl J Med 2020. NEJMoa2021436. doi:10.1056/NEJMoa2021436. |
| 43 | Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: An argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care 2020;24:128. |
| 44 | Tian S, Chang Z, Wang Y, Wu M, Zhang W, Zhou G, et al. Clinical characteristics and reasons of different duration from onset to release from quarantine for patients with COVID-19 outside Hubei province, China. MedRxiv. 2020. doi:10.1101/2020.03.21.20038778. |
| 45 | Tabibi S, Tabibi T, Conic RR, Banisaeed N, Streiff MB. Therapeutic plasma exchange: A potential management strategy for critically Ill COVID-19 patients. J Intensive Care Med 2020;35:827-35. |
| 46 | Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. Immunigenecity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults. Lancet 2020;396:479-88. |
| 47 | Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA vaccine against SARS-CoV-2 - preliminary report. N Engl J Med 2020;NEJMoa2022483. doi: 10.1056/NEJMoa2022483. |
| 48 | Van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR, et al. Safety and immunogenicity of the ChAdO×1 nCoV-19 vaccine against SARS-CoV-2. Nature 2020. doi: 10.1038/s41586-020-2608-y. |
| 49 | Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: The CORONADO study Published: August 2020; Diabetologia. 2020 Aug; 63 (8):1500–15. |
| 50 | Hsiang S, Allen D, Annan-Phan S, Bell K, Bolliger I, Chong T, et al. The effect of large-scale anti-contagion policies on the COVID-19 pandemic. Nature 2020. doi: 10.1038/s41586-020-2691-0. |
| 51 | Varatharaj A, Thomas N, Mark A Ellul MA, Davies NW, Pollak TA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: A UK-wide surveillance study. Lancet Psychiatry. 2020 June 25. doi.org/10.1016/S2215-0366(20)30287-x. Online ahead of print. |
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