|Year : 2020 | Volume
| Issue : 2 | Page : 43-48
COVID-19 news and views
Khalid Farooqui1, Adeel Ahmad Khan1, Abdel-Naser Elzouki2
1 Department of Medicine, Hamad Medical Corporation, Doha, Qatar
2 Department of Medicine, Hamad Medical Corporation, Doha; Weill Cornell Medical College-, Qatar
|Date of Submission||29-Apr-2020|
|Date of Acceptance||16-May-2020|
|Date of Web Publication||22-May-2020|
Dr. Khalid Farooqui
Department of Medicine, Al Khor Hospital, Hamad Medical Corporation, Doha
Source of Support: None, Conflict of Interest: None
The outbreak of Corona Virus disease 2019 (COVID-19) in December 2019 has spread around the world and become a global pandemic. It belongs to Beta coronavirus which also contains SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). There are lots of new studies coming up with update in pathophysiology, clinical manifestation, diagnostic tools, and newer medications and its action along with ongoing clinical trials. We are presenting a fast review about the COVID-19 from origin of the virus to the latest updates in management, so that physicians and health care providers across the globe can review latest news and views about the COVID-19 till date which can help in understanding the diagnosis and management of disease in this challenging time.
Keywords: Coronavirus, corona virus disease-2019, news, severe acute respiratory syndrome-coronavirus-2
|How to cite this article:|
Farooqui K, Khan AA, Elzouki AN. COVID-19 news and views. Libyan J Med Sci 2020;4:43-8
| Virology News and Views|| |
In December 2019, China reported the outbreak of corona virus disease-2019 (COVID-19); it has then spread around the world and become a global pandemic. The novel coronavirus (CoV) 2019 belongs to beta-Cov which also contains severe acute respiratory syndrome-CoV (SARS-CoV-2) and Middle East respiratory syndrome CoV (MERS-CoV). It is a single-stranded positive-sense RNA genome bound to a nucleoprotein (helical nucleocapsid) surrounded by a lipid layer envelope. Petal- or club-shaped spike glycoproteins project from the surface of envelope giving appearance of crown of thorns. The spike proteins get attached to the angiotensin-converting enzyme-2 (ACE-2) receptors present in type II pneumocytes in lungs and gastrointestinal tract and cause cell damage with intense inflammatory reaction.
Gattinoni et al. described phylogenetic analysis of 103 strains of SARS-CoV-2 from China; two different types of SARS-CoV-2 were identified: designated type L (accounting for 70% of the strains) and type S (accounting for 30%).
| Epidemiology News and Views|| |
Tang et al. described person-to-person spread as the main mode of transmission, mainly through respiratory droplets that typically do not travel more than six feet (about two meters) and do not linger in the air. van Doremalen et al. in one study had shown that SARS-CoV-2 can sustain in experimentally generated aerosols up to 3 h and present in air giving a more chance of rapid transmission. As per Chen et al., SARS-CoV-2 RNA has also been detected in blood and stool specimens. Latest correspondence published by Anfinrud et al. shows that SARS-CoV-2 can spread through airborne route in addition to droplet transmission. In view of uncertainty in transmission mechanism of SARS-COV2, airborne precautions were recommended in certain situations. Regarding of period of infectivity of the SARS-CoV-2, Zou et al. described the interval during which an individual with COVID-19 is infectious is uncertain. It appears that SARS-CoV-2 can be transmitted prior to the development of symptoms and throughout the course of illness.
The incubation period has been reported as 1–14 days.
Chin et al. measured stability of SARS-CoV-2 in different environmental conditions and also tested virucidal effects of disinfectants invitro. They concluded that at 4°, infectious titer of the virus decreased by only 0.7 log unit at around day 14. However, virus inactivation time decreased to 5 min when incubation temperature was raised to 70°. Overall, SARS-CoV-2 is highly stable in favorable environment, but it is very susceptible to standard disinfection methods.
| Diagnosis News and Views|| |
Using of polymerase chain reaction testing of nasopharyngeal and oropharyngeal swabs to diagnose severe acute respiratory syndrome-coronavirus-2 infection
Wang et al. reported that if only one polymerase chain reaction (PCR) swab testing is to be done, nasopharyngeal swab has more sensitivity than oropharyngeal swab. However, in patients with severe COVID-19 pneumonia, sputum or lower respiratory tract specimens via bronchoalveolar lavage are the ideal choices.
Detection of severe acute respiratory syndrome-coronavirus-2 RNA by polymerase chain reaction in fecal material and rectal swabbing of corona virus disease-2019-infected patients with pneumonia
Zhang et al.described that RNA of SARS-CoV-2 has also been detected in fecal material and rectal swabbing is an alternate mode of detection in patients with COVID-19 pneumonia.
Development of serological testing for the detection of severe acute respiratory syndrome-coronavirus-2
Serological assays for serum IgM and IgG antibodies have been developed. 50% of the patients become positive in 7 days and all the patients showed seroconversion in 14 days. Moreover, Chan et al. reported that SAR-CoV-2 has four structural proteins, namely, spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins. Antibodies against S proteins have been used in serological testing techniques.
Laboratory findings in patients infected with severe acute respiratory syndrome-coronavirus-2 and its correlation with disease severity
Several laboratory tests have recognized as helpful tools in the diagnosis of COVID-19 infection and correlated with the severity of infection-related pneumonia. [Table 1] summarizes these laboratory tests.
|Table 1: Laboratory markers correlating to disease severity for patients with corona virus disease-19 pneumonia|
Click here to view
Imaging findings in severe acute respiratory syndrome-coronavirus-2 pneumonia
As per the British Society Thoracic Imaging, the following features are apparent on radiological imaging.
Chest X-ray findings
- Typically, patchy ground-glass opacities peripheral and basal (unilateral in 25%)
- Number of lung segments increases with more severe disease
- Over time, patches coalesce into more dense consolidation
- May be subtle/appear normal (40%)
- Do not tend to see effusions (5%), cavitation, mass, and lymphadenopathy.
Chest computed tomography scan findings
- Sensitivity around 80% may be normal in early stages
- Peripheral ground-glass opacities
- Crazy paving may be present
- Diffuse alveolar damage
- Organizing pneumonia
- Less likely imaging findings: non-peripheral, effusions, lymph nodes
- Findings not seen in COVID-19 pneumonia: lobar pneumonia, cavitating lesions, tree-in bud changes.
According to the case series published from six hospitals in New York, myocardial injury with ST-segment elevation has been observed in patients with COVID-19. Myocardial injury in patients with COVID-19 could be due to plaque rupture, cytokine storm, hypoxic injury, coronary spasm, microthrombi, or direct endothelial or vascular injury.
| Treatment News and Views|| |
Approach and management of severe acute respiratory syndrome-coronavirus-2
Main issue is acute respiratory distress syndrome (ARDS), not shock, even if elevated lactate and BP is usually normal.
Consider antibiotics especially if there is suspicion of secondary bacterial infection.
Clinical trials are ongoing, e.g., remdesivir. Some antiviral drugs are being used which has proven benefits in reducing viral load.
May be harmful in early stages, increase viral shedding, but might be beneficial in ARDS and during cytokine storm phase of the disease.
The WHO says that so far, there is no definitive evidence of its effectiveness, although it is used in some countries for hospitalized patients and under closed in-hospital monitoring. The Food and Drug Administration (FDA) set up a large clinical trial.
(a) Target oxygen saturations 94%–98% (as per trust guidelines, unless if patients with COPD); (b) start with 2–4 L O2 via nasal cannula and progress to venturi and then nonrebreathe mask if required; (c) consider humidified oxygen (as many patients complaining of dry mouth); (d) if patient still hypoxic despite FiO2 >40%, escalate early to intensive care unit (ICU); and (e) Optiflow, CPAP, and BiPAP are not used routinely.
Early intubation should be considered in those it is indicated.
Renal failure occurs in 7%, and it is a strong predictor of mortality (92% acute tubular necrosis as part of multiorgan failure). Rhabdomyolysis may contribute.
Extracorporeal membrane oxygenation
ECMO is considered in young patients with single-organ failure
Hydroxychloroquine is a well-known drug with an anti-inflammatory activity that typically used for the treatment of malaria, systemic lupus erythematosus, or rheumatoid arthritis. It has also antiviral activitiesin vitro including interference with the cellular receptor ACE2 (potentially making it particularly effective against SARS and COVID-19), and impairment of acidification of endosomes, which interferes with virus trafficking within cells. It also has immunosuppressive properties with activity against many pro-inflammatory cytokines (e.g., interleukin [IL]-1 and IL-6) that might be helpful in prevention or treatment of cytokine storm.
Hydroxychloroquine with or without azithromycin as treatment for severe acute respiratory syndrome-coronavirus-2 infection
Gautret et al. conducted a nonrandomized, open-label study in France (Marseille study) evaluating the use of chloroquine (200 mg trice daily) with or without azithromycin (500 mg once daily, followed by 250 mg daily for 4 days). The primary endpoint was reduction in viral load. This was achieved, especially by the combination of chloroquine plus azithromycin. Study limitations include nonrandomization and withdrawal of some patients from the hydroxychloroquine group.
Chloroquine and hemoglobin metabolism in severe acute respiratory syndrome-coronavirus 2 infection
Wenzhong and Hualan found in anin vitro study that chloroquine could prevent orf1ab, ORF3a, and ORF10 proteins to attack the heme to form the porphyrin and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress.
Using of hydroxychloroquine as postexposure prophylaxis
Lee et al. reported that use of hydroxychloroquine as postexposure prophylaxis in a long-term care hospital in Korea showed negative test for COVID-19 with PCR in all the cases.
Grein et al. assessed the effects of 10-day course of remdesivir as compassionate use in patients with COVID-19 infection. 18-day follow-up showed improvement in oxygen support category in 68% of patients, 57% of patients receiving invasive mechanical ventilation were extubated, and 75% of patients on ECMO stopped requiring it. 28-day follow-up showed clinical improvement in 84% of cases. More recently, remdesivir being evaluated for the treatment of COVID-19 showed no difference in time to clinical improvement or mortality at 28 days among hospitalized patients with severe infection versus a control group, a draft abstract accidentally published by the WHO showed. The randomized trial, which was terminated prematurely due to poor accrual, found no difference between groups in time to clinical improvement compared with the control group (hazard ratio: 1.23, 95% confidence interval: 0.87–1.75) or mortality at 28 days (13.9% vs. 12.8%, respectively). The manuscript is now undergoing peer review before final publication.
CITRIS-ALI multicenter trial did appear to improve mortality in septic patients with severe acute respiratory failure. However, interpretation of this trial remains hopelessly contentious due to nearly unsolvable issues with survival-ship bias.
In a cohort study, Young et al. described 16 COVID-19 patients in Singapore. Among six patients with hypoxemia, five were treated with lopinavir/ritonavir (200 mg/100 mg BID, which is half of the usual dose of lopinavir). Among the five patients, two patients deteriorated and had persistent nasopharyngeal virus carriage. Possible reasons for these underwhelming results might include statistical underpowering, low dose of lopinavir/ritonavir, lack of synergistic ribavirin, and/or late initiation of therapy.
In another study, Cao et al. conducted an open-labeled randomized controlled trial comparing lopinavir + ritonavir (400/100 mg twice daily) for 14 days versus standard care alone. Results showed no significant statistical benefit with similar time of clinical improvement, 28 days mortality, and percentage with detectable viral load from throat swab.
Oseltamivir and other neuraminidase inhibitors
According to Tan et al., neuraminidase inhibitors including oseltamivir do not seem to work against SARS virus. Initial empiric therapy with neuraminidase inhibitors could be reasonable during influenza season in critically ill patients, if there is concern that the patient might have influenza pneumonia. Currently, in many locations, patients presenting with viral pneumonia are much more likely to have influenza than COVID-19.
A systematic review of 24 studies was conducted by Stockman et al. to assess the effect of ribavirin in patients with SARS infection. 20 studies were found to be inconclusive, while 4 studies showed possibility of even harmful effects namely hemolytic anemia (36%–61%) and derangement in liver enzymes.
Favipiravir is an RNA polymerase inhibitor that has been found to be effective against RNA viruses. Wenzhong and Hulalan postulated that ORF8 and surface glycoproteins could combine to the porphyrin to form the complex respectively. These proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will lead to less hemoglobin to carry oxygen and carbon dioxide. The lung cells have extremely intense inflammation due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images. According to these authors, favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins.
Chen et al. conducted a prospective, multicenter, open-labeled, randomized superiority trial comparing conventional treatment plus favipiravir versus conventional treatment plus arbidol (umifenovir used to treat influenza infection in China) for the treatment of patients with COVID-19 infection. No statistically significant difference was observed in clinical recovery rate after 7 days between the 2 groups.
Interferon-beta has shown effectiveness in patients with MERS infection, especially in combination with ritonavir or lopinavir–ritonavir. However, due to lack of clinical trials, their use in treatment of COVID 19 is not currently recommended.
Use of corticosteroids
Yang et al. conducted a meta-analysis of 15 studies involving 5270 patients about use of corticosteroids in patients with Cov infection. They concluded that corticosteroids use in patients with Cov infection was associated with higher mortality, longer length of stay, a higher risk of bacterial infection, and hypokalemia.
Tocilizumab is a monoclonal antibody against IL-6. Luo et al. conducted a study on 15 patients with SARS-CoV-2 infection who received tocilizumab. C-Reactive protein levels decreased in all patients. However, further effects on mortality benefit were inconclusive and needs further investigation.
The Food and Drug Administration-approved drug ivermectin inhibits the replication of severe acute respiratory syndrome-coronavirus-2 in vitro
Ivermectin is FDA-approved drug for parasitic infections. It has shown anin vitro antiviral properties against SARS-CoV-2 by reducing the viral RNA load around 5000-fold at 48 h.
Role of convalescent plasma in of severe acute respiratory syndrome-coronavirus-2 infection
It has been hypothesized that convalescent plasma from recovered patients containing neutralizing antibodies against the virus can help in treatment of COVID-19. Mair-Jenkins et al. conducted a meta-analysis of 32 studies of SARS-Cov and severe influenza virus infection. Administration of convalescent plasma resulted in statistically significant decrease in mortality as compared to no therapy (odds ratio = 0.25; 95% confidence interval = 14–45; I2 = 0%). A recent case series from China of five critically ill mechanically ventilated COVID-19 patients also showed encouraging results of using convalescent plasma. Three patients were extubated between day 2 and day 9 of plasma administration. Inflammatory markers showed improvement in all five patients and all the patients showed clearance of viremia between day 1 and day 12 after infusion.
In another study, Wu et al. analyzed plasma from 175 patients recovered from COVID-19 with mild symptoms. There was considerable degree of variability in the titers of neutralizing antibodies with antibody titers found to be higher in middle-age and elderly patients as compared to younger patients. Ten patients had neutralizing antibody titers under the detection levels. This shows that some patients might recover without developing high titers of neutralizing antibodies and stresses the need to assess antibody titers before using convalescent plasma for the treatment of COVID-19 patients. A study on effects of convalescent plasma in 10 severely ill patients with COVID-19 showed marked improvement in clinical status, blood oxygen levels, lymphocytes, CRP levels, and chest CT imaging findings.
Effect of Bacillus Calmette–Guerin Vaccine in corona virus disease 2019 prevention
The Bacillus Calmette–Guerin (BCG) vaccine used in many countries soon after birth of child to protect against severe tuberculosis infection has been hypothesized to be effective in preventing or decreasing severity of COVID-19 infection based on observation that countries without BCG vaccination policies are the ones most severely affected by COVID-19 pandemic. The WHO has recommended that there is no data currently supporting this hypothesis and further clinical trials are underway to assess this.
Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
In wake of COVID-19 infection, suggestions have been made to discontinue ACEIs and ARB in patients with suspected or proven COVID 19 infection citing that use of these drugs has the potential of altering ACE-2 activity leading to increase in virulence of CoVs as interaction between CoVs and ACE-2 has been hypothesized to play a role in infectivity of these viruses. Vaduganathan et al. concluded that data on effects of ACEIs and ARBs on ACE-2 expression in lungs are lacking. Hence, ACEIs and ARBs should be continued in patients with COVID 19 infection as benefits of continuing these medications outweigh the risks.
Venous thromboembolism prophylaxis in patients with corona virus disease-2019
Zhai et al. observed that nearly 20% of COVID 19 with severe or critically ill patients present with severe coagulopathy and concomitant venous thromboembolism is a potential cause of unexplained death. Panel of physicians and experts from China and Europe developed an opinion and evidence-based consensus on the prophylaxis as well as management of venous thromboembolism associated with COVID 19. Given the complexity of COVID 19 isolation, protection and supportive antithrombotic treatment are main challenges for the frontline physicians. Weight-based low-molecular-weight heparin (LMWH) enoxaparin is the first line of management in venous thromboembolism of COVID-19 critically ill patient unless contraindicated, alternatively can use unfractionated heparin infusion depending upon the severity of illness. Thromboprophylaxis is required in all ICU Patients choosing mainly LMWH with longer polysaccharide chain such as tinzaparin or dalteparin.
| Other News and Views|| |
Skin manifestations in corona virus disease-2019 infection
Like other viral infections, cutaneous manifestations have been observed in patients with SARS-CoV-2 infections as well. In an initial report, Sebastiano Recalcati, M. D., from the Alessandro Manzoni Hospital in Lecco, Italy, described skin manifestations in COVID-19 patients. In a total of 148 patients, about 20%–21% of patients develop cutaneous manifestation which commonly present as erythematous rash, widespread urticaria, and chickenpox-like vesicles, mostly involving the trunk region associated with mild or absent itching, and lesions usually healed in a few days.
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Conflicts of interest
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