20/06/2021
Updated on 20 June 2021
[Compiled by : Dr.Rakesh T Parakadavathu, Consultant- Infectious Diseases, Gimcare Hospital, Kannur, Kerala, India]
Tofacitinib: New arrival. Poor man’s Tocilizumab for treating cytokine storm, 10 mg twice daily for up to 14 days -meager benefits, very wide confidence intervals(1)
Monoclonal Antibody cocktail in seronegative criticaly ill patients: It was used (casirivimab and imdevimab, known as REGEN-COV2) as preventive, now proven benefit for oxygen dependent patients, who lacks antbody response.(2) The dose used in the trial is very high 8g but I believe 1200 mg would be enough
Vaccines being proven safe in pregnant(3)
Prophylactic-intensity anticoagulation preferred for critical illness or acute illness who do not have confirmed or suspected VTE (4)
Treatment of Multisystem Inflammatory Syndrome in Children: No difference in outcome between IVIg or steroids.(5)
TREATMENT
Proven Benefit
1. Dexamethasone in low dose: 6 mg OD, IV or PO x 10 days. Useful in critically ill patients. Reduce deaths by one-third in ventilated patients, one fifth in patients receiving oxygen, no benefit in stable patients.(6)
2. Tocilizumab: may be useful only in severe cases. 8 mg/kg q12 h IV, 2 doses.(7)(8)(9,10)
3. Remdesivir: Mild efficacy(11,11,12)
4. High dose steroids: More data needed. Small studies showing benefit.(13,14) Failed with MERS and Influenza.(15–17)
Proven Useless
5. Hydoxychloroquine: No strong evidence for benefit.(18,19) Randomized, controlled, open-label trial shows no use with Hydroxychloroquine(20)(21)
6. Ivermectine: In vitro only. Impossible dosing in humans to achieve required serum level. Trials going on.(18,19)
7. Lopinavir-Ritonavir : useless in COVID.(26
8. Convalescent plasma therapy: May not be useful. (23)Anecdotal reports showing benefits. 200 mL, donors with the neutralizing antibody titers above 1:640.(24–27)
Trials Ongoing
9. Favipiravir: In trials.
Testing
10. The rapid antigen test picks only 30% of positive patients.(3) The role is limited to use only in high probability setting where you can avoid a throat swab PCR in some, and also to prove that the person is not ‘infectious’ rather than ‘negative’.
11. Throat/Nasopharyngeal swab PCR: False-negative rate-100% on day 1 of exposure 38% on day 5, 20% at day 8, and 66% at day 21.(28)(29) Prolonged viral RNA detection unlikely to be infectious(30)
12. CT Chest: Sensitive (94%), but not specific.(31,32)
13. Antibodies(33): Seroconversion rate for Ab-93.1%, IgM-82.7% and IgG 64.7%.Median seroconversion time for Ab day-11, IgM day-12, IgG day-14,. Ab 150/ doubles in 24 hours or ferritin > 1500. (51)
32. Hydroxychloroquine + azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term, in rheumatoid arthritis patients (not with COVID)(52)
References (only for the truth seekers)
1. Guimarães PO, Quirk D, Furtado RH, Maia LN, Saraiva JF, Antunes MO, et al. Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med [Internet]. 2021 Jun 16 [cited 2021 Jun 20]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/34133856
2. RECOVERY trial finds Regeneron’s monoclonal antibody combination reduces deaths for hospitalised COVID-19 patients who have not mounted their own immune response — RECOVERY Trial [Internet]. [cited 2021 Jun 20]. Available from: https://www.recoverytrial.net/news/recovery-trial-finds-regeneron2019s-monoclonal-antibody-combination-reduces-deaths-for-hospitalised-covid-19-patients-who-have-not-mounted-their-own-immune-response-1
3. Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med. 2021 Jun 17;384(24):2273–82.
4. Cuker A, Tseng EK, Nieuwlaat R, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Adv [Internet]. 2021 Feb 9 [cited 2021 Jun 20];5(3):872–88. Available from: https://www.nih.gov/news-events/news-releases/nih-activ-trial-blood-thinners-pauses-
5. McArdle AJ, Vito O, Patel H, Seaby EG, Shah P, Wilson C, et al. Treatment of Multisystem Inflammatory Syndrome in Children. N Engl J Med [Internet]. 2021 Jun 16 [cited 2021 Jun 20];NEJMoa2102968. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2102968
6. Ezalia E, R IE, Elizabeth G, My WANH, Norhanim A, Wahidah A, et al. Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. Oxford Univ News Release [Internet]. 2020; Available from: http://dx.doi.org/10.1016/j.bpobgyn.2016.10.013%0Ahttps://doi.org/10.1016/j.solener.2019.02.027%0Ahttps://www.golder.com/insights/block-caving-a-viable-alternative/%0A???%0Ahttp://dx.doi.org/10.1016/j.hoc.2014.04.003%0Ahttp://www.moh.gov.my/penerbitan/CPG
7. Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol [Internet]. 2020 Jun [cited 2020 Jul 19];0(0). Available from: www.thelancet.com/rheumatologyPublishedonline
8. Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Jul 1;
9. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970–5.
10. Alzghari SK, Acuña VS. Supportive Treatment with Tocilizumab for COVID-19: A Systematic Review. J Clin Virol. 2020 Jun 1;127.
11. Singh AK, Singh A, Singh R, Misra A. Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies. Diabetes Metab Syndr Clin Res Rev. 2020 Jul 1;14(4):641–8.
12. Davies M, Osborne V, Lane S, Roy D, Dhanda S, Evans A, et al. Remdesivir in Treatment of COVID-19: A Systematic Benefit–Risk Assessment. Drug Saf. 2020;
13. Wang Y, Jiang W, He Q, Wang C, Wang B, Zhou P, et al. Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China [Internet]. medRxiv. Cold Spring Harbor Laboratory Press; 2020 Mar [cited 2020 Jun 21]. Available from: http://medrxiv.org/lookup/doi/10.1101/2020.03.06.20032342
14. Kolilekas L, Loverdos K, Giannakaki S, Vlassi L, Levounets A, Zervas E, et al. Can steroids reverse the severe COVID-19 induced “cytokine storm”? J Med Virol [Internet]. 2020 Jun 12 [cited 2020 Jun 21]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32530507
15. Delaney JW, Pinto R, Long J, Lamontagne F, Adhikari NK, Kumar A, et al. The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness. Crit Care. 2016 Mar 30;20(1).
16. Hui DS. Systemic Corticosteroid Therapy May Delay Viral Clearance in Patients with Middle East Respiratory Syndrome Coronavirus Infection. Am J Respir Crit Care Med [Internet]. 2018 Mar 15 [cited 2020 Jun 21];197(6):700–1. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29227752
17. Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, et al. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med [Internet]. 2018 Mar 15 [cited 2020 Jun 21];197(6):757–67. Available from: https://pubmed.ncbi.nlm.nih.gov/29161116/
18. Das S, Bhowmick S, Tiwari S, Sen S. An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19). Clinical Drug Investigation. Adis; 2020. p. 1.
19. Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020 May 7;
20. RECOVERY Collaborative Group, Horby P, Mafham M, Linsell L, Bell JL, Staplin N, et al. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med [Internet]. 2020 Oct 8 [cited 2020 Oct 14];NEJMoa2022926. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2022926
21. Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, et al. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. N Engl J Med [Internet]. 2020 Jul 23 [cited 2020 Aug 16]; Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2019014?query=recirc_mostViewed_railB_article
22. No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in RECOVERY — RECOVERY Trial [Internet]. 2020. [cited 2020 Jul 2]. Available from: https://www.recoverytrial.net/news/no-clinical-benefit-from-use-of-lopinavir-ritonavir-in-hospitalised-covid-19-patients-studied-in-recovery
23. Li L, Li L, Zhang W, Zhang W, Hu Y, Tong X, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA - J Am Med Assoc [Internet]. 2020 [cited 2020 Jul 19]; Available from: /pmc/articles/PMC7270883/?report=abstract
24. Rajendran K, Narayanasamy K, Rangarajan J, Rathinam J, Natarajan M, Ramachandran A. Convalescent plasma transfusion for the treatment of COVID-19: Systematic review. Journal of Medical Virology. John Wiley and Sons Inc.; 2020.
25. Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9490–6.
26. Ye M, Fu D, Ren Y, Wang F, Wang D, Zhang F, et al. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol. 2020;
27. Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19. JAMA [Internet]. 2020 Jun 3 [cited 2020 Jun 20]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2766943
28. Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med. 2020 May 13;
29. Woloshin S, Patel N, Kesselheim AS. False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications. N Engl J Med. 2020 Jun 5;
30. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 Apr 1;1–5.
31. Zhong L, Gong P, Biging GS. Diagnostic Performance of CT and Reverse Transcriptase-Polymerase Chain Reaction for Coronavirus Disease 2019: A Meta-Analysis. Radiology. 2012;78(May):1–15.
32. Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology [Internet]. 2020 Feb 12 [cited 2020 May 17];200343. Available from: http://pubs.rsna.org/doi/10.1148/radiol.2020200343
33. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020 Mar 28;
34. Hurt AC, Wheatley AK. Neutralizing antibody therapeutics for covid-19 [Internet]. Vol. 13, Viruses. MDPI AG; 2021 [cited 2021 Jun 20]. Available from: /pmc/articles/PMC8067572/
35. Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med [Internet]. 2020 Jun 3 [cited 2020 Jun 21]; Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
36. Radonovich LJ, Simberkoff MS, Bessesen MT, Brown AC, Cummings DAT, Gaydos CA, et al. N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel: A Randomized Clinical Trial. JAMA [Internet]. 2019 Sep 3 [cited 2020 Jun 19];322(9):824–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31479137
37. Long Y, Hu T, Liu L, Chen R, Guo Q, Yang L, et al. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. 2020 May 1;13(2):93–101.
38. Smith JD, MacDougall CC, Johnstone J, Copes RA, Schwartz B, Garber GE. Effectiveness of N95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: A systematic review and meta-analysis. CMAJ. 2016 May 17;188(8):567–74.
39. COVID-19 Decontamination and Reuse of Filtering Facepiece Respirators | CDC [Internet]. [cited 2020 Jun 21]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/ppe-strategy/decontamination-reuse-respirators.html
40. Poletti P, Tirani M, Cereda D, Trentini F, Guzzetta G, Sabatino G, et al. Probability of symptoms and critical disease after SARS-CoV-2 infection. 2020 Jun 15 [cited 2020 Jun 29]; Available from: http://arxiv.org/abs/2006.08471
41. Li J, Wang X, Chen J, Zhang H, Deng A. Association of Renin-Angiotensin System Inhibitors with Severity or Risk of Death in Patients with Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020;
42. Fosbøl EL, Butt JH, Østergaard L, Andersson C, Selmer C, Kragholm K, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA [Internet]. 2020 Jun 19 [cited 2020 Jun 25]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32558877
43. Merkler AE, Parikh NS, Mir S, Gupta A, Kamel H, Lin E, et al. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. JAMA Neurol [Internet]. 2020 Jul 2 [cited 2020 Jul 7]; Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2768098
44. Das LT, Abramson EL, Kaushal R. Reopening US Schools in the Era of COVID-19: Practical Guidance From Other Nations. JAMA Heal Forum [Internet]. 2020 Jun 1 [cited 2020 Jul 7];1(6):e200789–e200789. Available from: https://jamanetwork.com/channels/health-forum/fullarticle/2767982
45. Abbas K, Procter SR, van Zandvoort K, Clark A, Funk S, Mengistu T, et al. Routine childhood immunisation during the COVID-19 pandemic in Africa: a benefit–risk analysis of health benefits versus excess risk of SARS-CoV-2 infection. Lancet Glob Heal [Internet]. 2020 Jul [cited 2020 Jul 19];0(0). Available from: https://linkinghub.elsevier.com/retrieve/pii/S2214109X20303089
46. Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, Del Prato S. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol [Internet]. 2020 Jul [cited 2020 Jul 19];0(0). Available from: https://linkinghub.elsevier.com/retrieve/pii/S2213858720302382
47. Plenge RM. Molecular Underpinnings of Severe Coronavirus Disease 2019. JAMA [Internet]. 2020 Jul 24 [cited 2020 Jul 25]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2768925
48. Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. JAMA [Internet]. 2020 Jul 20 [cited 2020 Jul 25]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2768715
49. To KK-W, Hung IF-N, Ip JD, Chu AW-H, Chan W-M, Tam AR, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis [Internet]. 2020 Aug 25 [cited 2020 Aug 27]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32840608
50. Galanti M, Shaman J. Direct Observation of Repeated Infections With Endemic Coronaviruses. J Infect Dis [Internet]. 2020 Jul 7 [cited 2020 Aug 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/32692346/
51. Manson JJ, Crooks C, Naja M, Ledlie A, Goulden B, Liddle T, et al. COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. Lancet Rheumatol [Internet]. 2020 Aug [cited 2020 Aug 27];0(0). Available from: https://linkinghub.elsevier.com/retrieve/pii/S2665991320302757
52. Lane JCE, Weaver J, Kostka K, Duarte-Salles T, Abrahao MTF, Alghoul H, et al. Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study. Lancet Rheumatol [Internet]. 2020 Aug [cited 2020 Aug 27];0(0). Available from: https://linkinghub.elsevier.com/retrieve/pii/S2665991320302769
