The following is a literature review I conducted on various topics related to the arguments catalogue. Please be aware that this is a literature review. It is certainly possible to suggest, for example, that there are biases in what is possible to publish or what scientists prefer to study, the fact of which might be a critical foundation for some arguments. Nonetheless, that will not be described here.
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According to the WHO, current evidence indicates that COVID-19 primarily spreads through respiratory droplets among people in close contact with one another (2020). For this reason, methods that prevent the spread of such droplets would substantially reduce the risk of infection and so it may be expected for masks to be effective on a theoretical level.
Limited direct epidemiological evidence exists for the use of masks. First, one observational study exists on the effect of masks on COVID-19 specifically, a retrospective cohort study which examined the reduction in secondary infections through face-mask use in Beijing households, which found that “face mask use by the primary case and family contacts before the primary case developed symptoms was 79% effective in reducing transmission” (Wang et al., 2020). However, this study did not distinguish between different types of masks. Furthermore, this result may not generalize to different societies and cultures. Another study, a systematic review sponsored by the WHO, found that mask use had a protective effect, but only reviewed studies of masks’ effects on SARS transmission (Chu et al., 2020). One controlled trial of mask use on influenza control exists, which found a protective effect even despite low compliance and noted that in a pandemic situation compliance would improve (MacIntyre et al., 2020). Finally, a randomized controlled trial on the effects of adding a mask recommendation to other public health measures indicated that the difference in infection rates between the control and experimental groups was not statistically significant, although “the 95% CIs are compatible with a 46% reduction to a 23% increase in infection” (Bundgaard et al., 2020). Again, it is not necessarily possible to generalize the results of this study to different societies and cultures. Furthermore, although it is true that the result was not statistically significant, the study size was only sufficient to detect a 50% or greater reduction, which may have been too great.
A cluster randomized trial specifically examining the effects of cloth masks to medical masks in hospital healthcare workers in Vietnam found that the rates of all infection outcomes were highest with cloth masks and that “penetration of cloth masks by particles was almost 97% and medical masks 44%” (MacIntyre et al., 2015). Once again, it may not be appropriate to generalize this result to different locations, and while cloth masks were less effective they did not appear to be totally ineffective. Furthermore, a study examining risk compensation in Americans indicates that Americans who wear masks spend an average of 11-24 minutes more outside of the home and “increase visits to some commercial locations—most notably restaurants, which are a high-risk location” (Yan et al., 2021).
The effects of mask use on SARS and influenza transmission cannot necessarily be generalized to COVID-19 but they nonetheless generally support the effectiveness of medical mask use in reducing the spread of respiratory illnesses. Evidence on cloth masks appears inconclusive, but cloth masks may be appropriate for use on an individual level. However, in terms of policy, the effectiveness of mask recommendations or mandates is unproven.
Many different vaccines for COVID-19 currently exist, including the Pfizer-BioNTech vaccine, the Moderna vaccine, the Oxford-AstraZeneca vaccine, Sputnik V, etc. This review will focus primarily on the safety and efficacy of vaccines available for use in the United States, namely the Pfizer-BioNTech and Moderna COVID-19 vaccines.
A two-dose regimen of the Pfizer-BioNTech vaccine “conferred 95% protection against Covid-19 in persons 16 years of age or older”, with “safety over a median of 2 months… similar to that of other viral vaccines”, as indicated from the phase 2/3 part of the trial (Polack et al., 2020). Similarly, the preliminary analysis results of the ongoing phase 3 trial of the Moderna COVID-19 vaccine reported “94.1% efficacy at preventing Covid-19 illness” and that “no safety concerns were identified” (Baden et al., 2021). However, a prominent limitation of both studies is that they excluded individuals diagnosed with immunocompromising conditions from participation. Furthermore, these trials did not examine how the vaccines would affect transmission of the disease and were unable to examine long-term safety implications.
Despite this, it is most likely that vaccines will reduce virus transmission and that they are safe in the long-term (Sax, 2021). First, in the Moderna trial, participants underwent testing multiple times, and fewer infections were found in the experimental group at week four. Second, population-based studies indicate that people without symptoms are less likely to transmit the virus. Long-term side effects from vaccines are also generally very rare. Still, no fully conclusive evidence exists here.
Hydroxychloroquine alone is clearly not effective for treating COVID-19. Some observational studies have observed a link between hydroxychloroquine use and mortality reduction (Castelnuovo et al., 2020; Ip et al., 2021). However, such studies are easily subject to confounders (Horby & Emberson, 2020). In contrast, multiple randomized controlled trials have not found hydroxychloroquine to be effective in treating COVID-19 (Barnabas et al., 2020; Beltran-Gonzalez et al., 2021; Boulware et al., 2020). These studies did not find hydroxychloroquine to be unsafe, however.
Critics of such trials claim that hydroxychloroquine must be administered very early in order to be effective and the period of administration used within such studies is too long or hydroxychloroquine must be used in concert with other treatments such as zinc supplementation. It does not appear that randomized controlled trials using these exact specifications exist. A preprint of an observational study indicated that zinc supplementation in addition to hydroxychloroquine was significantly more effective than hydroxychloroquine alone (Carlucci et al., 2020). However, again, such studies are easily subject to confounders. A further study experimentally demonstrated a potential mechanism through which hydroxychloroquine could be effective when used in concert with a TMPRSS2 inhibitor (Ou et al., 2021).
No randomized controlled trials have been conducted to test the efficacy of lockdown-type measures for reasons that are self-evident. Nonetheless, observational studies on the effectiveness of lockdowns do exist. Islam et al. (2020) draws from daily reported cases in 149 countries to determine that various lockdown-type measures were associated with a decrease of 13% in COVID-19 incidence. Chaudhry et al. (2020) also suggests that lockdowns were significantly associated with increased patient recovery rates. A preprint by Kepp & Bjørnskov (2021) suggests, in contrast, that in some circumstances “efficient infection surveillance and voluntary compliance make full lockdowns unnecessary” based on information gathered from selective lockdowns in Northern Denmark. However, observational studies are again easily confounded, especially when examining the effects of policy. Conclusive evidence for the efficacy of lockdown-type policies does not exist.
Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., … Zaks, T. (2021). Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. New England Journal of Medicine, 384(5), 403–416. https://doi.org/10.1056/nejmoa2035389
Barnabas, R. V., Brown, E. R., Bershteyn, A., Stankiewicz Karita, H. C., Johnston, C., Thorpe, L. E., … Baeten, J. M. (2020). Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Annals of Internal Medicine. https://doi.org/10.7326/m20-6519
Beltran-Gonzalez, J. L., Gonzalez-Gamez, M., Mendoza-Enciso, E.-A., Esparza-Maldonado, R. J., Hernanez-Palacios, D., Duenas-Campos, S., … Guerra, J. M. A. A. (2021, February 23). Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial. medRxiv. https://doi.org/10.1101/2021.02.18.21252037.
Boulware, D. R., Pullen, M. F., Bangdiwala, A. S., Pastick, K. A., Lofgren, S. M., Okafor, E. C., … Hullsiek, K. H. (2020). A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. New England Journal of Medicine, 383(6), 517–525. https://doi.org/10.1056/nejmoa2016638
Carlucci, P. M., Ahuja, T., Petrilli, C., Rajagopalan, H., Jones, S., & Rahimian, J. (2020, May 8). Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients. medRxiv. https://doi.org/10.1101/2020.05.02.20080036.
Castelnuovo, A. D., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bruno, R., … Iacoviello, L. (2020). Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study. European Journal of Internal Medicine, 82, 38–47. https://doi.org/10.1016/j.ejim.2020.08.019
Chaudhry, R., Dranitsaris, G., Mubashir, T., Bartoszko, J., & Riazi, S. (2020). A country level analysis measuring the impact of government actions, country preparedness and socioeconomic factors on COVID-19 mortality and related health outcomes. EClinicalMedicine, 25. https://doi.org/10.1016/j.eclinm.2020.100464
Chu, D. K., Duda, S., Solo, K., Yaacoub, S., & Schunemann, H. (2020). Physical Distancing, Face Masks, and Eye Protection to Prevent Person-to-Person Transmission of SARS-CoV-2 and COVID-19: A Systematic Review and Meta-Analysis. Journal of Vascular Surgery, 72(4), 1500. https://doi.org/10.1016/j.jvs.2020.07.040
Coronavirus disease (COVID-19): How is it Transmitted? (2020, October 20). https://www.who.int/news-room/q-a-detail/coronavirus-disease-covid-19-how-is-it-transmitted.
Horby, P. W., & Emberson, J. R. (2020). Hydroxychloroquine for COVID-19: Balancing contrasting claims. European Journal of Internal Medicine, 82, 25–26. https://doi.org/10.1016/j.ejim.2020.11.018
Ip, A., Ahn, J., Zhou, Y., Goy, A. H., Hansen, E., Pecora, A. L., … Goldberg, S. L. (2021). Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study. BMC Infectious Diseases, 21(1). https://doi.org/10.1186/s12879-021-05773-w
Islam, N., Sharp, S. J., Chowell, G., Shabnam, S., Kawachi, I., Lacey, B., … White, M. (2020). Physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries. BMJ. https://doi.org/10.1136/bmj.m2743
Kepp, K. P., & Bjørnskov, C. (2021, January 4). Lockdown Effects on Sars-CoV-2 Transmission – The evidence from Northern Jutland. medRxiv. https://doi.org/10.1101/2020.12.28.20248936.
MacIntyre, C. R., Dwyer, D., Seale, H., Fasher, M., Booy, R., Cheung, P., … Browne, G. (2008). The First Randomized, Controlled Clinical Trial of Mask Use in Households to Prevent Respiratory Virus Transmission. International Journal of Infectious Diseases, 12. https://doi.org/10.1016/j.ijid.2008.05.877
MacIntyre, C. R., Seale, H., Dung, T. C., Hien, N. T., Nga, P. T., Chughtai, A. A., … Wang, Q. (2015). A cluster randomised trial of cloth masks compared with medical masks in healthcare workers. BMJ Open, 5(4). https://doi.org/10.1136/bmjopen-2014-006577
Ou, T., Mou, H., Zhang, L., Ojha, A., Choe, H., & Farzan, M. (2021). Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. PLOS Pathogens, 17(1). https://doi.org/10.1371/journal.ppat.1009212
Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., … Gruber, W. C. (2020). Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine, 383(27), 2603–2615. https://doi.org/10.1056/nejmoa2034577
Sax, P. (2021, February 17). Covid-19 Vaccine Frequently Asked Questions. https://www.nejm.org. https://www.nejm.org/covid-vaccine/faq.
Van Dyke, M. E., Rogers, T. M., Pevzner, E., Satterwhite, C. L., Shah, H. B., Beckman, W. J., … Rule, J. (2020, December 31). Trends in County-Level COVID-19 Incidence in Counties With and Without a Mask Mandate - Kansas, June 1–August 23, 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/volumes/69/wr/mm6947e2.htm?s_cid=mm6947e2_w.
Wang, Y., Tian, H., Zhang, L., Zhang, M., Guo, D., Wu, W., … MacIntyre, C. (2020). Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China. BMJ Global Health, 5(5). https://doi.org/10.1136/bmjgh-2020-002794
Yan, Y., Bayham, J., Richter, A., & Fenichel, E. P. (2021). Risk compensation and face mask mandates during the COVID-19 pandemic. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-82574-w
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