Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis.

Background: Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern. Objective and Methods: To estimate the efficacy and safety of COVID-19 therapeutics, we performed meta-analyses of the studies reporting clinical features and treatments of COVID-19 published from January 21 to September 6, 2020. Results: We included 136 studies that involved 102,345 COVID-19 patients. The most prevalent treatments were antibiotics (proportion: 0.59, 95% CI: [0.51, 0.67]) and antivirals (proportion: 0.52, 95% CI: [0.44, 0.60]). The combination of lopinavir/ritonavir and Arbidol was the most effective in treating COVID-19 (standardized mean difference (SMD) = 0.68, 95% CI: [0.15, 1.21]). The use of corticosteroids was associated with a small clinical improvement (SMD = -0.40, 95% CI: [-0.85, -0.23]), but with a higher risk of disease progression and death (mortality: RR = 9.26, 95% CI: [4.81, 17.80]; hospitalization length: RR = 1.54, 95% CI: [1.39, 1.72]; severe adverse events: RR = 2.65, 95% CI: [2.09, 3.37]). The use of hydroxychloroquine was associated with a higher risk of death (RR = 1.68, 95% CI: [1.18, 2.38]). The combination of lopinavir/ritonavir, ribavirin, and interferon-ß (RR = 0.34, 95% CI: [0.22, 0.54]); hydroxychloroquine (RR = 0.58, 95% CI: [0.39, 0.58]); and lopinavir/ritonavir (RR = 0.72, 95% CI: [0.56, 0.91]) was associated with reduced hospitalization length. Hydrocortisone (RR = 0.05, 95% CI: [0.03, 0.10]) and remdesivir (RR = 0.74, 95% CI: [0.62, 0.90]) were associated with lower incidence of severe adverse events. Dexamethasone was not significant in reducing disease progression (RR = 0.45, 95% CI: [0.16, 1.25]) and mortality (RR = 0.90, 95% CI: [0.70, 1.16]). The estimated combination of corticosteroids with antivirals was associated with a better clinical improvement than antivirals alone (SMD = -1.09, 95% CI: [-1.64, -0.53]). Conclusion: Antivirals are safe and effective in COVID-19 treatment. Remdesivir cannot significantly reduce COVID-19 mortality and hospitalization length, while it is associated with a lower incidence of severe adverse events. Corticosteroids could increase COVID-19 severity, but it could be beneficial when combined with antivirals. Our data are potentially valuable for the clinical treatment and management of COVID-19 patients.

Corona vaccine review / Koronavírusvakcina-vademecum.

Összefoglaló. A SARS-CoV-2 okozta megbetegedés (COVID-19) a cikk megírásáig a világon több mint 82 millió embert érintett, a halálos áldozatok száma 1,8 millió (2,2%). Hazánkban eddig 300 000 feletti esetszámot regisztráltak, a cikk megjelenésének idején már várhatóan több mint 10 000 halottal (3%). Habár a megbetegedésnek oki gyógyszeres terápiája egyelore nincs, egyes antivirális szerek és a rekonvaleszcens plazma alkalmazása a tapasztalatok szerint csökkentik a vírusterhelést, és ezzel hozzájárulnak a beteg gyógyulásához. Az eddig példa nélküli epidemiológiai rendelkezések nem tudták megállítani, csak lelassítani a betegség terjedését, ezért a megelozés tunik az egyetlen, a közeljövoben tömegek számára is elérheto megoldásnak. A jelen cikk nem egy virológiai vagy biotechnológiai szakmunka, sokkal inkább egy összefoglaló házi- és általános orvosok számára, amely ismerteti a jelenleg engedélyezett, illetve a közeljövoben forgalomba kerülo védooltások elonyeit és hátrányait a COVID-19 tágabb kontextusában. Írásunkban bemutatjuk a leggyakoribb álhíreket, rémhíreket is, valamint ezek cáfolatát is annak érdekében, hogy kollégáink felkészültebben tudják betegeiket informálni, valamint segíteni a vakcináció fontosságával kapcsolatos döntéshozatalt. Egy járvány megfékezésének legkézenfekvobb módja a társadalmi szintu védettség megvalósítása. A nyájimmunitás kialakulása nélkül nagy valószínuséggel e jelenlegi pandémia sem állítható meg. Amennyiben egyéni és társadalmi szinten is vissza szeretnénk térni a vírus elotti életünkhöz, újra élvezve az akadálytalan áru- és kereskedelmi forgalom jelentette elonyöket, akkor a tömeges oltás tunik a leghatékonyabb eszköznek ennek eléréséhez. A fertozo betegségek számának és mortalitásának a 20. században tapasztalt jelentos csökkenése egyértelmuen a társadalmi szintu átoltottságnak, valamint a higiénés körülmények javulásának köszönheto. Az oltás ugyan önkéntes, de felvételének kérdése pandémiás helyzetben valószínuleg nemcsak egyéni döntés, de társadalmi felelosségvállalás kérdése is. Orv Hetil. 2021; 162(8): 283-292. Summary. Out of more than 82 million people worldwide, 1.8 million (2.2%) succumbed to SARS-CoV-2 disease (COVID-19). In 2020, more than 300 000 cases were registered in Hungary, and by the time of publication of this article, the death toll would probably exceed 10 000 (3%). Currently no causative drug therapy is available, however, observational evidence suggests that certain antivirals and the use of convalescent plasma may change the disease course. The unprecedented, strict epidemiological provisions managed to slow down the spread of the disease though they could not stop it. It seems that prevention remains the only readily available option to beat COVID-19. This is not a virology or biotechnology paper, but an unbiased review for general practitioners, aiming to summarize the advantages/disadvantages of the (emergency) authorized and soon-to-be-launched vaccines in the wider context of COVID-19. We also intended to address and debunk the most common misconceptions, aiming to help both doctors and patients to make a fact-based, informed decision about vaccination. Herd immunity is paramount to combat COVID pandemic. Without population-level vaccination, we are unlikely to regain the quality of life, the freedom of travel and the unrestricted economy/commerce we enjoyed before. It is obvious that the significant reduction in morbity/mortality of infectious diseases in the 20th century was achieved through advancements in vaccinology and improved hygiene. Albeit voluntary, vaccination in a pandemic situation is probably not only an individual decision, but social responsibility as well. Orv Hetil. 2021; 162(8): 283-292.

Immune response scenario and vaccine development for SARS-CoV-2 infection.

COVID-19 pandemic has started in December 2019 in China and quickly extended to become a worldwide health and economic emergency issue. It is caused by the novel coronavirus; SARS-CoV-2. COVID-19 patients' clinical presentations vary from asymptomatic infection or flu like symptoms to serious pneumonia which could be associated with multiple organ failure possibly leading to death. It is understood that the immune response to SARS-CoV-2 includes all elements of the immune system which could altogether succeed in viral elimination and complete cure. Meanwhile, this immune response may also lead to disease progression and could be responsible for the patient's death. Many trials have been done recently to create therapies and vaccines against human coronavirus infections such as MERS or SARS, however, till now, there is some controversy about the effectiveness and safety of antiviral drugs and vaccines which have been developed to treat and prevent this disease and its management depends mainly on supportive care. The spike glycoprotein or protein S of SARS-CoV-2 is the main promoter that induces development of neutralizing antibodies; hence, many attempts of vaccines and antiviral drugs development have been designed to be directed specifically against this protein. While some of these attempts have been proved to be efficient in in vitro settings, only few of them have been proceeded to randomized animal trials and human studies which makes COVID-19 prevention an ongoing challenge. This review describes the natural immune response scenario during COVID-19 and the vaccines development trials to create efficient vaccines thus helping to build more effective approaches for prophylaxis and management.

Multicenter Initial Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection.

Coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses increase oxidative stress in the body leading to cellular and tissue damage. To combat this, administration of high-dose vitamin C (ascorbic acid or ascorbate), in addition to standard conventional supportive treatments, has been shown to be a safe and effective therapy for severe cases of respiratory viral infection. Morbidity, mortality, infectiveness and spread of infectious diseases are dependent on the host-pathogen relationship. Given the lack of effective and safe antiviral drugs for coronaviruses, there should be more attention in supporting host immune defence, cytoprotection and immunoregulation. Implementation of high-dose vitamin C therapy could dramatically reduce the need for high doses of corticosteroids, antibacterials and antiviral drugs that may be immunosuppressive, adrenal depressive and toxic, complicating the disease course. In order to effectively fight the novel SARS-CoV-2 virus, medical professionals should explore readily available pharmaceutical and nutritional therapeutic agents with proven antioxidant, anti-inflammatory and immunosupportive properties. Supplemental vitamin C may also provide additional benefits for the prevention of viral infections, shorten the disease course and lessen complications of the disease.