Most of drugs could have certain mucocutaneous reactions and COVID‐19 drugs are not an exception that we focused. We systematically reviewed databases until August 15, 2020 and among initial 851 articles, 30 articles entered this study (20 case reports, 4 cohorts, and 6 controlled clinical trials). The types of reactions included AGEP, morbiliform drug eruptions, vasculitis, DRESS syndrome, urticarial vasculitis, and so on. The treatments have been used before side effects occur, included: antimalarial, anti‐viral, antibiotics, tocilizumab, enoxaparin and and so on. In pandemic, we found 0.004% to 4.15% of definite drug‐induced mucocutaneous reactions. The interval between drug usage and the eruption varied about few hours to 1 month; tightly dependent to the type of drug and hydroxychloroqine seems to be the drug with highest mean interval. Antivirals, antimalarials, azithromycin, and tocilizumab are most responsive drugs for adverse drug reactions, but antivirals especially in combination with antimalarial drugs are in the first step. Types of skin reactions are usually morbilliform/exanthematous maculopapular rashes or urticarial eruptions, which mostly may manage by steroids during few days. In the setting of HCQ, specific reactions like AGEP should be considered. Lopinavir/ritonavir is the most prevalent used drug among antivirals with the highest skin adverse reaction; ribarivin and remdisivir also could induce cutaneous drug reactions but favipiravir has no or less adverse effects. Logically the rate of dermatologic adverse effects among anivirals may relate to their frequency of usage. Rarely, potentially life‐threatening reactions may occur. Better management strategies could achieve by knowing more about drug‐induced mucocutaneous presentations of COVID‐19.

Objectives Earlier diagnosis and the best management of virus‐related, drug‐related or mixed severe potentially life‐threatening mucocutaneous reactions of COVID‐19 patients are of great concern. These patients, especially hospitalised cases, are usually in a complicated situation (because of multi‐organ failures), which makes their management more challenging. In such consultant cases, achieving by the definite beneficial management strategies that therapeutically address all concurrent comorbidities are really hard to reach or even frequently impossible. Methods According to the lack of any relevant systematic review, we thoroughly searched the databases until 5 October 2020 and finally found 57 articles including 93 patients. It is needed to know clinical presentations of these severe skin eruptions, signs and symptoms of COVID in these patients, time of skin rash appearance, classifying drug‐related or virus‐related skin lesions, classifying the type of skin rash, patients’ outcome and concurrent both COVID‐19 therapy and skin rash treatment. Result Severe and potential life‐threatening mucocutaneous dermatologic manifestations of COVID‐19 usually may be divided into three major categories: virus‐associated, drug‐associated, and those with uncertainty about the exact origin. Angioedema, vascular lesions, toxic shock syndrome, erythroderma, DRESS, haemorrhagic bulla, AGEP, EM, SJS and TEN, generalised pustular figurate erythema were the main entities found as severe dermatologic reactions in all categories. Conclusion We can conclude vascular injuries may be the most common cause of severe dermatologic manifestations of COVID‐19, which is concordant with many proposed hypercoagulation tendencies and systemic inflammatory response syndrome as one of the most important pathomechanisms of COVID‐19 so the skin may show these features in various presentations and degrees.

Background: The COVID-19 infection is a novel virus that mainly targets the respiratory system via specific receptors without any coronavirus-targeted therapies. Many efforts have been made to prepare specific vaccines for COVID-19 or use of prefabricated vaccines of other similar viruses, especially severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza (flu). We aimed to evaluate the effects of previous flu vaccine injection on severity of incoming COVID-19 infection. Methods: We conducted a large cross-sectional study of 529 hospitalized Iranian COVID patients to evaluate the severity of disease courses in patients with or without previous flu vaccination history using some main factors like length of hospitalization, need for the intensive care unit (ICU) admission and length of stay in the ICU for comparison between COVID-19 infected patients with or without flu vaccination history. For the quantitative data, we used independent-samples t and Mann-Whitney tests. The qualitative data were calculated using the Fisher exact and chi-square tests in IBM SPSS Statistics version 22 (SPSS Inc) and P value <0.05 was considered statistically significant. Results: There were no significant differences in the demographic data of patients, disease, and severity-related parameters between the 2 groups. It means that there were not any significant differences between patients with and without history of flu vaccination regarding mean days of hospitalization, percentage of needing to be admitted to the ICU, days being admitted to the ICU (8.44±6.36 vs 7.94±8.57; 17% vs 11.5%; and 1.17±3.09 vs 0.92±3.04, retrospectively) (p=0.883, 0.235, and 0.809, respectively). In the laboratory tests, in comparison between patients with and without history of previous flu vaccination, only lymphocytes count in the vaccine positive group was higher than the vaccine negative group (20.82±11.23 vs 18.04±9.71) (p=0.067) and creatine phosphokinase (CPK) levels were higher in the vaccine negative group (146.57±109.72 vs 214.15±332.06) (p=0.006). Conclusion: We did not find any association between flu vaccination and decrease in disease severity in our patients. It seems that patients with previous history of flu vaccination may experience less laboratory abnormalities in some parameters that could be interpreted in favor of lower overall inflammation; however, this study cannot answer this definitely because of its design. As we collected retrospective data from only alive discharged patients and had no healthy control group, we could not discuss the probable effect of the vaccine on the mortality rate or its probable protective role against the infection. We need more well-designed controlled studies with different populations in different geographic areas to address the controversies.

This narrative review article was conducted to lay out a summarized but exhaustive review of current literature over mucocutaneous manifestations in 4 dimensions of SARS‐CoV‐2 pandemic: virus itself, treatment‐related, vaccine‐induced, and alteration of chronic dermatologic diseases following infection. Virus and vaccine‐related were mainly self‐limited and non‐severe. Treatment‐related reactions could be life‐threatening.

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